Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment.

Adult hippocampal neurogenesis has been demonstrated in several species and is regulated by both environmental and pharmacological stimuli. The present study seeks to determine whether hippocampal proliferation and neurogenesis are altered in adult animals exposed to inescapable shock (IS) in the learned helplessness model of depression. We report that exposure to avoidance testing, regardless of pre-exposure to IS, decreases cell proliferation in the hippocampus, extending previous studies demonstrating downregulation of neurogenesis by exposure to acute stressors. In addition, when the analysis was conducted 9 days after exposure to IS we observed a significant decrease in cell proliferation compared to nonshocked animals. Administration of fluoxetine, a serotonin selective reuptake inhibitor, from days 2-8 blocked the downregulation of cell proliferation resulting from IS. Fluoxetine treatment also reversed the deficit in escape latency observed in animals exposed to IS. Finally, at the 9 day time point, there was no significant difference in blood levels of corticosterone between nonshocked and IS exposed animals, indicating that the decreased cell proliferation that is observed is not due to increased levels of this adrenal steroid. These findings demonstrate that exposure to IS, which results in a state of behavioral despair, decreases hippocampal cell proliferation and that this effect can be reversed by fluoxetine treatment.     

Controlled release of sugar and toxicant from a novel device for controlling pest insects

A novel biodegradable device, designed for long-lasting residual effectiveness of feeding stimulant (sugar) and insecticide (dimethoate) against apple maggot flies and other insects, was formulated. The device is an 8-cm diameter fruit-mimicking sphere, consisting of 42–50% sugar entrapped in a mixture of gelatinized corn flour and wheat flour in the presence of glycerin, and coated with a layer of latex paint containing dimethoate and sugar. We found that the outer layer of paint prevents cracking of the sphere upon drying and creates a barrier to control the release of both sugar and dimethoate. Releases of each ingredient were screened first by chemical analysis and then by bioassays in the laboratory and in field cages against apple maggot flies. Chemical analysis demonstrated strong potential for controlled release of water-soluble feeding stimulant and water-insoluble insecticide measured as a function of the amount of rainfall and duration of exposure time. Field results showed greater than 70% insecticidal activity after 11 weeks of sphere exposure in an orchard. This device has the potential to be used for a variety of insect-control applications through manipulating its shape, color and texture into forms known to be attractive to target insects, and by employing various toxicants designed to be effective against such insects.     

Quantitative and comparative study of haematoporphyrin-derived photosensitizers on a murine tumour model

Eight commercially available HPD-photosensitizers intended for photodynamic therapy were tested in a murine tumour model with regard to their therapeutic efficacy. The regrowth delay of the fibrosarcoma SSK-2 on the mouse C3H, Neuherberg-line, was determined 3, 24, 48 and 72 h after injection of the drugs (dose: 9 mg kg^–1 body weight). The corresponding pharmacodynamics, as measured by regrowth delay, were approximated by an exponential function and the characterizing coefficients derived. These coefficients served to quantify the photodynamic properties of the drugs.The pharmacodynamics of five substances were compared with those obtained fluorometrically. The latter showed shorter decay constants than the therapy-correlated substances which indicates different metabolic behaviour of the therapeutic and diagnostically useful fluorescent components of haematoporphyrin-derived photosensitizers.     

MANAGEMENT OF CHONDROSARCOMA INCLUDING MODULAR CERAMIC AND ALUMINA PROSTHETIC REPLACEMENT

Forty-one cases of chondrosarcoma from varying sites throughout the body, and treated exclusively by one of the authors (R. L. H.) from 1972 to 1990 were reviewed. The symptoms, signs, location of tumours, treatment and progress are presented. Particular attention was paid to modular bone replacement techniques. Excision and reconstruction of the bone or joint were carried out in 17 femora, five tibia and six humeri. Comparison between this method of management and other techniques is discussed. Titanium and alumina prostheses for the hip, femur, tibia, shoulder and humerus have been designed by the senior author. These are both inert and modular, and have been found to be superior to other methods of treatment in both function and cosmesis. They do not possess the same potential donor infection risks and other disadvantages of allograft replacement. Immediate postoperative weight bearing and mobilization are possible with these systems. The Huckstep prostheses allow for bony in growth into their porous coated alumina sleeves, spacers and stems. In addition, the titanium alloy locking component for the femoral stems has an elasticity half that of other metal alloys and this was found to minimize stress shielding.     

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.     

Physical and Sexual Abuse and their Relation to Psychiatric Disorder and Suicidal Behavior among Adolescents who are Psychiatrically Hospitalized

Adolescents who were psychiatrically hospitalized ( N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.     

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GAB_A receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABA_A receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc.     

A specific and sensitive radioimmunoassay for rat C-peptide

A sensitive and specific radioimmunoassay for rat serum C-peptide (RCP) has been developed and validated using a guinea pig anti-rat C-peptide antibody to synthetic rat C-peptide. Negligible crossreactivity (<0.01%) to human proinsulin was observed, whereas human insulin, human pancreatic polypeptide (hPP), porcine insulin, porcine C-peptide, bovine insulin, rat insulin, porcine-PP, and glucagon, respectively, did not produce measurable displacement of RCP tracer. Human C-peptide even in a supraphysiological concentration range crossreacted poorly (<0.1%). The sensitivity limit of the assay calculated at ±3 standard deviations was 24.2pM (0.07 ng/mL). RCP standard concentrations ranged from 25–1600pM. The intraassay-and between assay-coefficient of variations (CV) were 3.5–6.1% and 4.1–9.5%, respectively. The mean percentage recovery of RCP added to rat serum samples was 100.8±2%. Serum volume dilution from 25 to 100 μL did not significantly alter the expected RCP level. Migration of rat serum C-peptide and that of synthetic RCP were identical in a Sephadex G-50 chromatographic analysis. The mean fasting and postprandial plasma RCP levels in normal rats were 102±15pM and 485±75pM, respectively. RCP levels following intravenous glucose tolerance test in diabetic and nondiabetic rats were consistent with expected patterns. In conclusion, we have developed and validated a rat C-peptide assay that is sensitive, simple, and specific for RCP in serum. The assay provides a reliable tool for studies of diabetes using rodent animal models.     

Group Similarities in Beliefs Concerning the Causes of Alcohol Problems and the Effectiveness of Means of Overcoming Problem Alcohol Use

Four hundred and eight respondents, who did or did not know persons close to themselves with alcohol problems, from four different racial/ethnic groups (with one group, Filipinos, categorized in terms of whether they were born in the Philippines or in the US.) rated the importance of 19 different causes of problem alcohol use and 22 different means of overcoming problem alcohol use. Rank-order correlations across sexes, persons differing in exposure to problem drinkers, and ethnic groups were nearly all in the 0.90's regarding causation. Correlations of Caucasians' ratings with those of other groups were high, but only in the 0.60's and 0.70'9, chiefly because Caucasians were more prone to regard problem alcohol use as hereditary and as a disease, and less likely to believe problem use to result from social factors. All across-group correlations concerning beliefs about the effectiveness of means of overcoming problems were in the 0.90's. Some of the means of treatment regarded most highly by all groups have not been demonstrated to be effective.     

Differential effects of kindling and kindled seizures on place learning in the morris water maze

There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.