In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell proliferation.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of hematopoietic stem cell proliferation, is known to reduce in vivo the damage resulting from treatment with chemotherapeutic agents or ionizing radiation on the stem cell compartment. Recently, AcSDKP has been shown to be a physiological substrate of the N-active site of angiotensin I-converting enzyme (ACE). Four analogs of the tetrapeptide expressing a high stability towards ACE degradation in vitro have been synthesized in order to provide new molecules likely to improve the myeloprotection displayed by AcSDKP.

Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study.

In recent years, the startle reflex has become an exciting new tool to investigate affective responses to aversive stimuli in humans. The popularity of this methodology is largely based on the substantial amount of animal research available on this topic. Several procedures have been developed to examine startle potentiation in humans, but most studies have been carried out in adults and may not be appropriate for children or adolescents.

Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test.

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

Background: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested.

Methods: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition.

Fear-potentiated startle in adolescent offspring of parents with anxiety disorders.

Background: The startle reflex and its potentiation by aversive states was used as a possible vulnerability marker for anxiety disorders in adolescent offspring of parents with this condition.

Methods: The participants were 39 low-risk adolescents (16 male/23 female) with a parental history of no psychiatric disorder and 35 high-risk adolescents (18 male/17 female) with a parental history of anxiety disorders. The magnitude of startle was examined at baseline and during anticipation of an aversive stimulus (fear-potentiated startle).

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth.

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

Objective: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness.

Regulation of Arousal and Attention in Preschool Children Exposed to Cocaine Prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth.

Effects of threat of shock, shock electrode placement and darkness on startle.

Fear can be elicited by physically-presented explicit threat stimuli or by more static contextual stimuli that are not an immediate source of danger. Research in both humans and animals suggest that fear produced by these two types of stimuli represents separate processes mediated by different brain structures. The present study used the startle reflex methodology to examine affective responses elicited by an explicit threat cue signalling a period of shock anticipation and by two types of contextual stimuli; darkness and attaching the shock electrodes.

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP or Goralatide), a physiological regulator of hematopoiesis, inhibits the entry into the S-phase of murine and human hematopoietic stem cells. It has been shown to reduce the damage to specific compartments in the bone marrow resulting from treatment with chemotherapeutic agents, ionizing radiations, hyperthermy, or phototherapy. The present study was performed to assess the therapeutic potential of AcSDKP in vivo in reducing both the toxicity and the hematopoietic damage induced by fractionated administration of doxorubicin (DOX), a widely used anticancer drug.

Effects of stress and shock anticipation on prepulse inhibition of the startle reflex.

The effects of shock anticipation and attention to external stimuli on prepulse inhibition (PPI) were compared. In the threat-of-shock experiment, acoustic startle stimuli were presented with and without prepulses when aversive shocks were or were not anticipated. In the control experiment, startle and prepulse stimuli were delivered during periods with attended or ignored external stimuli.

Darkness facilitates the acoustic startle reflex in humans.

The effects of darkness on startle reactivity and prepulse inhibition were investigated in two studies with 25 subjects participating in each study. Acoustic startle stimuli that were or were not preceded by an acoustic prepulse were delivered in alternating periods of complete darkness or light. In both studies, darkness significantly increased the magnitude of startle but did not affect prepulse inhibition (PPI).

Startle reflex abnormalities in women with sexual assault-related posttraumatic stress disorder.

Objective: This investigation was designed to assess the acoustic startle response in treatment-seeking women with sexual assault-related posttraumatic stress disorder (PTSD).

Method: Thirteen patients with sexual assault-related PTSD and 16 healthy female comparison subjects were recruited for participation in the study. Each patient met the full criteria for PTSD according to the Structured Clinical Interview for DSM-III-R.

Fear-potentiated startle conditioning in humans: explicit and contextual cue conditioning following paired versus unpaired training.

Conditioned fear in response to explicit and contextual cues was examined using the startle reflex in three groups of participants over two sessions separated by 4-5 days. The conditioned stimulus (CS) was paired with an aversive unconditioned stimulus (US) (shock) during conditioning in the paired but not in the unpaired group. In the reaction time (RT) group, the US was a nonaversive visual signal for an RT task.

Startle modulation in children at risk for anxiety disorders and/or alcoholism.

Objective: To examine the startle reflex as a possible vulnerability marker among offspring of parents with anxiety disorders and/or alcoholism.

Method: The subjects were 66 male and female offspring (aged 10 to 17 years) of proband who participated in a family study of comorbidity of alcoholism and anxiety disorders. Testing consisted of examining the startle reflex and its modulation by prepulse stimuli (prepulse facilitation and prepulse inhibition).

Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-chlorophenylpiperazine (mCPP).

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.

Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder.

Although an exaggerated startle response is a symptom of posttraumatic stress disorder (PTSD), empirical support for elevated baseline startle in PTSD has been weak. The present study investigated the eyeblink component of the acoustic startle reflex and prepulse inhibition (PPI) in 21 unmedicated Vietnam veterans with PTSD and in 17 civilian and 10 combat veteran comparison subjects. Patients with PTSD exhibited normal acoustic startle amplitude, but showed a significant reduction in PPI relative to the civilian subjects.

The psychobiological basis of posttraumatic stress disorder.

Posttraumatic stress disorder is a disorder with an identifiable etiological factor (exposure to a traumatic event) and with a complex symptomatology (i.e. intrusive memories, avoidance, hyperarousal) that suggests dysfunction in multiple psychobiological systems.

The antiproliferative activity of the tetrapeptide Acetyl-N-SerAspLysPro, an inhibitor of haematopoietic stem cell proliferation, is not mediated by a thymosin beta 4-like effect on actin assembly.

Acetyl-N-SerAspLysPro (AcSDKP), known as a negative regulator of haematopoiesis, has been principally reported as an inhibitor of haematopoietic pluripotent stem cell proliferation. The tetrapeptide sequence is identical to the N-terminus of thymosin beta 4 (T beta 4), from which it has been suggested that it may be derived. Recently, evidence was shown that T beta 4 plays a role as a negative regulator of actin polymerization leading to the sequestration of its monomeric form.

Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis.

Impaired sensory gating and increased distractibility are key information-processing deficits in schizophrenia. This study evaluated the hypothesis that distractibility is related to reduced sensory gating. Performance on vigilance and distractibility tasks was compared to prepulse inhibition (PPI) of the acoustic startle reflex in 28 stable chronic psychotic patients.

Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder.

Objective: Exaggerated startle reflex is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to assess the magnitude of the acoustic startle reflex in Gulf War veterans with PTSD.

Method: The eye-blink component of the startle reflex was measured in response to six blocks of pseudorandomized 40-msec white noise bursts of varying intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD, seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD.

Fear-potentiated startle in posttraumatic stress disorder.

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls.