31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients

Most research with 31P-magnetic resonance spectroscopy (31P-MRS) in affective disorders has been done in the field of bipolar disturbances. Reduced frontal and temporal lobe phosphomonoester (PME) concentrations were measured in the euthymic state, whereas increased values were found in the depressed state. In bipolar-II patients reduced phosphocreatine (PCr) concentrations were reported in the euthymic, depressed, and manic state. The aim of the present study was to explore whether PME and PCr were also altered in the frontal lobe of major depressed, unipolar patients. Therefore, we used 31P-MRS to investigate the relative phospholipid and high-energy phosphate concentrations in the frontal lobe of 14 unipolar patients, mostly medicated, and 8 age-matched controls. We found increased PME and decreased ATP values. Other 31P-MRS parameters were not different in both groups. Phosphomonoester percentages correlated negatively with the degree of depression. Thus, the main alterations found in bipolar depressed patients could also be demonstrated in unipolar depressed patients. The results are discussed with regard to disturbed phospholipid and intracellular high-energy phosphate metabolism in depressed patients.     

The effects of triethanolamine myristate, a fatty acid salt, on the bioavailability of riboflavin in dogs

A study in dogs was performed in which a physiologic approach to delaying gastric emptying was examined. Triethanolamine myristate (a fatty acid salt) was used to delay gastric emptying in hopes of increasing the bioavailability of riboflavin. A bilayer tablet consisting of triethanolamine myristate and riboflavin resulted in an absolute bioavailability of 2-3 times greater than the bioavailability of riboflavin alone. Increases in bioavailability although to a lesser extent, were also seen with the 30 min pretreatment with triethanolamine myristate. The results suggest that it was possible to delay gastric emptying.     

Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines

Escherichia coli leader peptidase, an integral membrane protein, is responsible for the cleavage of the signal sequence of many exported proteins. Recent studies suggest that it is a novel serine protease that utilizes a serine-lysine catalytic dyad. In an effort to further understand the mechanism of this enzyme, an internally quenched fluorescent peptide substrate incorporating the leader peptidase cleavage site of maltose binding protein signal peptide, Y(NO2)-F-S-A-S-A-L-A-K-I-K(Abz) (anthraniloyl), was designed and synthesized. In the intact peptide, the fluorescence of the anthraniloyl group is quenched by the 3-nitrotyrosine. This quenched fluorescence is liberated upon cleavage of the peptide by the leader peptidase, resulting in increased fluorescence that could then be monitored fluorometrically. The designed substrate can be cleaved effectively by E. coli leader peptidase as detected by both HPLC and fluorescent spectroscopy. Mass spectra of cleavage products demonstrated that the cleavage occurs at the predicted site (A-K). The cleavage of the peptide substrate has a linear dependence on the enzyme concentration (0.1 to 1.9 microM) and the kcat/K(m) was calculated to be 71.1 M-1 s-1. These data are comparable with the unmodified peptide substrate. This report represents the first direct continuous assay based on fluorescence resonance energy transfer for E. coli leader peptidase.     

Inhibition of hemopoiesis in vitro by neuroblastoma-derived gangliosides

Hemopoiesis is disturbed in bone marrow-involving cancers like leukemia and neuroblastoma. Shedding of gangliosides by tumor cells may contribute to this tumor-induced bone marrow suppression. We studied in vitro the inhibitory effects of murine neuroblastoma cells (Neuro-2a and C1300) and their gangliosides on hemopoiesis using normal murine hemopoietic progenitor colony-forming assays. Transwell cultured neuroblastoma cells showed a dose-dependent inhibition on hemopoiesis, indicating that a soluble factor was responsible for this effect. Furthermore, the supernatant of Neuro-2a cultured cells inhibited hemopoietic proliferation and differentiation. To determine whether the inhibitory effect was indeed due to shed gangliosides and not, for instance, caused by cytokines, the effect of DL-threo-1 -phenyl-2-decanoylamino-3-morpholino-1-propanol (DL-PDMP) on Neuro-2a cells was studied. DL-PDMP is a potent inhibitor of glucosylceramide synthase, resulting in inhibition of the synthesis and shedding of gangliosides. The initially observed inhibitory effect of supernatant of Neuro-2a cells was abrogated by culturing these cells for 3 days in the presence of 10 microM DL-PDMP. Moreover, gangliosides isolated from Neuro-2a cell membranes inhibited hemopoietic growth. To determine whether the described phenomena in vitro are a reflection of bone marrow suppression occurring in vivo, gangliosides isolated from plasma of neuroblastoma patients were tested for their effects on human hemopoietic progenitor colony-forming assays. These human neuroblastoma-derived gangliosides inhibited normal erythropoiesis (colony-forming unit-erythroid/burst-forming unit-erythroid) and myelopoiesis (colony-forming unit-granulocyte/macrophage) to a higher extent compared with gangliosides isolated from control plasma. Altogether these results suggest that gangliosides shed by neuroblastoma cells inhibit hemopoiesis and may contribute to the observed bone marrow depression in neuroblastoma patients.     

Micromechanical models for the Brownian motion of hair cell stereocilia

Brownian motion of the hairs (stereocilia) of amphibian hair cells has been shown in experiments to be in the range of some nm. Our models of the Brownian motion of coupled harmonic oscillators with mechanical properties of stereocilia lead to similar displacements. Computer simulation shows that stochastic fluctuations enhance the encoding of low level acoustic signals. Stochastic resonance lowers the detection threshold of auditory signals to amplitudes one order of magnitude lower than that of the Brownian motion.     

Noniatrogenic esophageal trauma

Few guidelines are available with which to facilitate treatment in patients with noniatrogenic injuries of the esophagus. Early diagnosis and proper management are essential if a good outcome is to be expected. In an effort to define better the treatment of patients with penetrating and blunt injuries of the esophagus, we report our recent 5-year experience at an urban trauma center. From July 1988 to June 1993, nineteen patients with esophageal perforations from penetrating (18) and blunt (1) trauma were identified by our trauma registry. There was no mortality in this group of patients and morbidity was mostly due to associated injuries. Eleven cervical esophageal injuries were repaired. One cervical injury was treated by stopping oral intake and giving intravenous antibiotics. The neck was not drained in 10 of the surgical cases. In 1 patient a tracheoesophageal fistula developed, which later was repaired with a pectoralis muscle flap. Seven perforations were identified in the thoracic (2) and abdominal (5) portions of the esophagus. All were due to gunshot wounds. In 4 cases, a fundal wrap was used to reinforce the repairs. Postoperative contrast studies confirmed that all repairs were intact. We conclude that penetrating and blunt tears of the esophagus can be repaired safely with minimal mortality. Morbidity is usually from associated injuries such as to the spinal cord and trachea. When identified early, cervical esophageal injuries do not need to be drained routinely.     

Disruption of mesectodermal lineages by temporal misexpression of the Drosophila POU-domain transcription factor, drifter

The horizontal and vertical considerations that must be taken into account during the diagnosis and subsequent treatment of the dentally and skeletally compromised patient are discussed. The treatment planning and treatment of a difficult malocclusion that required comprehensive orthodontics with surgical intervention are presented.     

Oxidative stress following traumatic brain injury in rats

BACKGROUND: Free radicals may be involved in the pathophysiology of traumatic brain injury (TBI) through oxidative damage of neurovascular structures. Endogenous antioxidants, such as ascorbate and alpha-tocopherol, may play a critical role in combating these oxidative reactions and their oxidized products can serve as an important index of oxidative stress. METHODS: We used electron spin resonance (ESR) spectroscopy and in vivo spin trapping (reaction of an organic compound with free radical species) to detect the possible generation of free radicals after TBI. Injury was inflicted by a weight drop technique over the head (5.7 kg-cm). Rats were intravenously infused with either 1 mL, 0.1 M of the spin trap, alpha-phenyl-N-tert-butyl nitrone (PBN), or an equivalent volume of saline immediately before TBI or sham-injury. Animals were divided into four groups: (1) Group I: PBN-infused sham-injured, (2) Group II: PBN-infused injured, (3) Group III: saline-infused sham-injured, and (4) Group IV: saline-infused injured. Additional groups of saline-infused uninjured, saline-infused, and PBN-infused injured animals were used for histopathology. Sixty minutes after TBI or sham-injury, rats were again anesthetized and decapitated. The brains were removed within 1 minute, homogenized, and extracted for lipids. The extracts were analyzed by ESR spectroscopy. Brain ascorbic acid (AA) concentration was determined spectrophotometrically, using the ascorbate oxidase assay. RESULTS: No PBN spin adduct signals (indicating trapped free radical species) were visible 60 minutes after TBI. All groups of rats showed an ascorbyl free radical signal. The ascorbyl signal intensity (AI) was, however, significantly higher in the injured rats, while the brain (AA) was significantly reduced. In addition, the ratio of AI/AA, which eliminates the effect of variable ascorbate concentrations in the brain, was also significantly higher in the injured animals. CONCLUSIONS: We conclude that 60 minutes following TBI there was a significantly increased level of oxidative stress in the brain. This may reflect formation of free radical species with subsequent interaction with ascorbate (antioxidant) during the 60 minute period. The lack of PBN spin adduct signals 1 hour after TBI may indicate that free radical generation is time dependent and might be detectable earlier or later than the 60 minute period.     

Biochemical and molecular homogeneity in the patellar tendon of the immature pig

Patellar tendon is widely used for reconstruction of the anterior cruciate ligament. However, few studies have investigated the tendon's homogeneity, a characteristic often assumed of it in experiments. In this study, the assumption that the patellar tendon is homogeneous was tested by dividing the central half of the tendon into six sections along its length and width and comparing commonly measured biochemical parameters and patterns of gene expression among these sections. No significant differences were found between the sections for any of the studied parameters: water content (p > 0.5), DNA content (p > 0.9), total collagen content (p > 0.8), amount of type I collagen (p > 0.7) or type-III collagen (p > 0.7), or expression of mRNA (p > 0.9). For all parameters, the minimum power value for statistical analyses was greater than 0.80. It was concluded that the central half of the tendon is homogeneous in terms of all of the measured parameters. The results provide important information for the many experiments that sample part of the patellar tendon to infer the characteristics of the whole tendon, e.g., biopsy studies.