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Biomedical subjects

S Schreiber

Publications and source records attributed to S Schreiber.

At least 19 recordsLinked to original sources
PubMed1997

Augmentation of opioid induced antinociception by the atypical antipsychotic drug risperidone in mice.

Risperidone is a novel atypical neuroleptic with a favorable profile of side effects due to its unique pharmacological activity: it exhibits both potent dopamine D2 and 5-HT2 receptor blocking activity, as well as high affinity for alpha1 and alpha2 adrenergic receptors and histamine H1 receptor. We found that risperidone has a potent antinociceptive effect in the tailflick assay with an ED50 of 26.4 mg/kg. This effect of risperidone was antagonized by naloxone (P < 0.05). This sensitivity to naloxone indicates that at least some of the analgesic effects of risperidone are mediated by an opioid mechanism of action. beta-FNA (mu1 mu2-antagonist), naloxonazine (mu1-antagonist) and norbinaltorphamine (nor-BNI; kappa1-analgesia) reversed risperidone antinociceptive effect (P < 0.05). Naltrindole (delta-antagonist) only partially reversed risperidone antinociceptive effect. We found that the sensitivity of risperidone antinociceptive effect to selective antagonists implies involvement of mu1-, mu2- and kappa1-opioid and to a lesser extent delta-opioid mechanisms. These results suggest a possible role for risperidone both in the management of pain and in the management of opiate withdrawal and detoxification.

Animals↗
PubMed1997

Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa 3 analgesia.

Buprenorphine is a mixed opioid agonist/antagonist analgesic. This study was designed to determine the role of opioid receptor subtypes, especially kappa 3, in buprenorphine-induced analgesia in mice. Buprenorphine, when injected systemically, revealed a potent analgesic effect by tailflick assay, with a biphasic dose-response curve, which was reversed by naloxone. The presence of analgesic cross-tolerance between buprenorphine and naloxone benzoylhydrazone (NalBzoH) and morphine indicated a role for kappa 3 and mu receptor subtype in buprenorphine analgesia. Additional studies with selective opioid antagonists indicated kappa 1 mechanisms of action. We did not detect any involvement of the delta receptor subtype. Low doses of buprenorphine antagonized morphine analgesia, while high doses of buprenorphine coadministered with morphine elicited increasing analgesia in a dose-dependent manner. These findings suggest that buprenorphine elicits analgesia through an interaction with kappa 3 receptors and to a lesser extent with kappa 1 as well as its activity as partial mu receptor agonist.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning".

A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: "chemical preconditioning." The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 +/- 27% (mean +/- SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1-24 h prior to slice preparation (preconditioned slices), psap improved to 90 +/- 15% (p < 0.01). Posthypoxic oxygen free radicals were reduced to 65 +/- 10% (mean +/- SD) of control in preconditioned slices (p < 0.05). Posthypoxic neuronal density improved from 52 +/- 15% (mean +/- SD) in control slices to 97 +/- 23% in preconditioned slices (p < 0.001). Glibenclamide, an antagonist at KATP-channels, partly reversed increased hypoxic tolerance. We conclude that chemical preconditioning induces early-onset long-lasting tolerance against in vitro hypoxia. Ultimately, this strategy may be applicable as a neuroprotective strategy in humans.

Adenosine Triphosphate↗
PubMed1997

High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors.

Seminal viral load is likely to be directly related to the sexual transmissibility of human immunodeficiency virus type 1 (HIV-1). However, it is not clear whether the level of HIV-1 in semen varies with the stage of infection and whether antiretroviral therapy reduces seminal viral load. A nucleic acid sequence-based amplification (NASBA) technique was used to quantify HIV-1 RNA as an indicator of infectious viral load in semen and blood plasma of homosexual men with different stages and durations of HIV-1 infection. The median viral load in a cross section of 34 men was 11,000 HIV-1 RNA copies/ml (range, <400 to 1.3 x 10(7) copies/ml) in whole semen and 5,238 HIV-1 RNA copies/ml (range, <400 to 2.8 x 10(5) copies/ml) in seminal plasma, which is 10- to 1,000-fold higher than previous estimates. Viral loads in whole semen and seminal plasma were strongly correlated with blood plasma viral load (P < 0.001) but not with blood CD4+ T-cell count (P = 0.420). Longitudinal analysis of eight subjects who progressed to AIDS showed that seminal viral load increased in most cases, with viral load consistently higher in blood plasma than in semen. Viral loads in semen and blood plasma decreased markedly in six other patients following initiation of potent combination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inhibitor (DMP-266). These findings have important implications for the biology of sexual transmission of HIV-1 and its potential reduction by antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease.

Adult↗
PubMed1997

Gastric mucus of the guinea pig: proton carrier and diffusion barrier.

Proton transport with the gastric mucus was investigated in the guinea pig in vitro by use of three experimental series. In series I, pH profiles were obtained in the mucus and mucosa of a gastric explant with fine-tipped double-barreled microelectrodes. With a luminal pH of 1.8, pH increased across this layer to approximately 6 at the epithelial surface. Thickness of the gastric mucous gel layer increased continuously by 170 +/- 100 microns/h in the unstimulated and by 450 +/- 120 microns/h in the histamine-stimulated preparation (means +/- SD). In series II, fresh guinea pig gastric mucus was obtained from the gastric mucosa and titrated at 10 degrees C from pH 6.5 to 0.7, followed by an incubation period of 30 min at 37 degrees C. During this incubation period, a spontaneous acidic shift was observed, corresponding to a proton release from the mucus of 130 +/- 19 mM. This proton release could be blocked by the pepsin inhibitor pepstatin and was not observed when titrating down to only pH 3. Buffer values calculated as the mean slope of the titration curves in the pH range of 7 to 3 averaged 40 mM/pH unit. In series III, when titration was repeated with purified porcine mucin, no proton release was observed during incubation at pH 1.0, unless pepsinogen (375 U/ml) had been added before titration. Proton release during incubation at pH 1.0 and 37 degrees C in the presence of pepsinogen averaged 50 mM. The data suggest that protons secreted by the gastric mucosa are buffered by the continuously secreted mucus and transported, bound to the proteins of the mucus, toward the gastric lumen. During this transport, pepsinogen is converted within the mucus to pepsin. Pepsin modifies the buffering properties of the mucus, whereby protons are released from the protein binding. Thus the mucus forms a vehicle for proton transport toward the gastric lumen while, at the same time, constituting a diffusion barrier to prevent proton backdiffusion toward the gastric epithelium.

Animals↗
PubMed1996

Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.

BACKGROUND: Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels in such patients. METHODS: Thirty-four patients with inflammatory bowel disease (15 with ulcerative colitis and 19 with Crohn's disease) and anemia refractory to iron therapy (hemoglobin concentrations below 10.0 g per deciliter [6.2 mmol per liter]) were randomly assigned in a prospective, double-blind, 12-week trial to receive either oral iron (100 mg per day) and subcutaneous erythropoietin (150 U per kilogram of body weight twice per week) (n=17) or oral iron and placebo (n=17). The primary measure of efficacy was an increase in hemoglobin levels of more than 1.0 g per deciliter (0.62 mmol per liter). Additional analyses were performed with other patients with inflammatory bowel disease. RESULTS: The severity of anemia was related to clinical disease activity as well as to in vitro monocyte secretion of interleukin-1 beta, a proinflammatory cytokine. Serum erythropoietin concentrations were increased in 52 randomly selected outpatients with inflammatory bowel disease and anemia, but the concentrations were inadequate in relation to the degree of anemia. Twelve weeks of therapy with recombinant erythropoietin and oral iron increased mean (+/-SE) hemoglobin concentrations from 8.81+/-0.27 g per deciliter (5.47+/-0.17 micromol per liter) to 10.52+/-0.41 g per deciliter (6.5+/-0.25 micromol per liter), whereas hemoglobin concentrations in the placebo group decreased from 8.69+/-0.11 g per deciliter (5.4+/-0.068 micromol per liter) to 7.84+/- 0.33 g per deciliter (4.9+/-0.2 mmol per liter) (P<0.001). After 12 weeks, hemoglobin levels had increased by more than 1.0 g per deciliter in 82 percent of the patients in the erythropoietin group, as compared with 24 percent of those in the placebo group (P=0.002). There were five treatment failures in the placebo group and two in the erythropoietin group (P=0.18); treatment failure was defined as a decrease in hemoglobin levels of more than 2.0 g per deciliter (1.24 micromol per liter) to a value below 8.0 g per deciliter (4.96 micromol per liter) or any decrease to less than 6.5 g per deciliter (4.03 micromol per liter). CONCLUSIONS: In patients with inflammatory bowel disease and anemia refractory to treatment with iron and vitamins, treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels.

Adolescent↗
PubMed1996

Effects of sodium fluoride and alendronate on the bone mineral in minipigs: a small-angle X-ray scattering and backscattered electron imaging study.

Sodium fluoride (NaF), which stimulates bone formation, and bisphosphonates, which reduce bone resorption, are both used in the treatment of osteoporosis, and are binding to bone mineral. In this study, using small-angle X-ray scattering and backscattered electron imaging, we analyzed the bone mineral in the vertebrae of minipigs treated with fluoride, with the bisphosphonate alendronate (ALN), or with vehicle. All specimens were investigated blindly. A slight increase in the average thickness of the mineral crystals as well as changes in the structure of the mineral/collagen composite were found in the case of fluoride-treated animals. No differences were found between ALN-treated animals and controls. The changes produced by fluoride are in the same direction as seen in bones from patients treated with NaF, albeit much smaller. They also correlate quantitatively with the reduction in biomechanical properties of bone in fluoride-treated minipigs found in an earlier study with the same animals. These findings suggest that small changes in the structure of the mineral/collagen composite in bone may considerably affect its biomechanical properties. It also emphasizes the delicate balance between the increase of bone mass and deterioration of bone material properties for the effect of fluoride on the biomechanical properties of bone.

Alendronate↗
PubMed1996

Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions.

Possible roles of the complement (C) system in the normal and injured brain were explored with inbred mice that carried a frameshift mutation in the C5 gene. A congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5-deficient (C5-) B10.D2/oSnJ with the Hc0 allele from the C5-deficient DBA/2J donor strain. In response to the excitotoxin kainic acid (KA), C5- mice had more hippocampal pyramidal neuron death and greater induction of astrocyte mRNAs (GFAP, apoE, apoJ). In primary astrocyte cultures from unlesioned mice, an inflammatory stimulus (LPS) caused greater production of IL-6 and TNF production in C5- mice. These enhanced responses to KA and LPS suggest that hereditary C5 deficits modify responses to neurodegenerative stimuli of neurons and astrocytes. Moreover, unlesioned C5- mice had smaller input-output slopes for the NMDA component of the EPSP amplitude, but enhanced the Ca(+2)-dependent AMPA binding. Thus, C5 deficits also modify basal properties of glutamatergic neurotransmission that pertain to synaptic plasticity. These findings are also discussed in relation to roles of the C-system in Alzheimer disease (AD). C5 deficiencies may also be considered in the choice of strains as transgene hosts and for genetic analysis of normal and pathological brain functions. In recent transgenic studies for AD, C5- hosts showed greater neurodegeneration, consistent with the present data. These pleiotropic associations of C5 deficiency indicate roles for the C-system in neurodegeneration, but also in normal neural functions.

Animals↗
PubMed1996

Characterization of bone mineral crystals in horse radius by small-angle X-ray scattering.

The size and the orientation of the bone salt (mineral) crystals in the cranial and caudal zones in the transverse midshaft section of the equine radius were investigated by small-angle X-ray scattering (SAXS). The results are interpreted as indicating that the crystals had an elongated shape with an average thickness of T = 3.17 +/- 0. 15 nm in the caudal region and T = 3.79 +/- 0.20 nm in the cranial region. Their orientation was predominantly in the longitudinal direction of the bone. There was no preferential orientation within the transverse plane. The distribution of tilt angles with respect to the longitudinal direction was determined directly from the SAXS data: the average angle was about 30 degrees for the cranial region and 45 degrees for the caudal region. Assuming that the needle-like crystals are parallel with the collagen fibrils, the angular distribution of the crystals is in good agreement with previous measurements of collagen orientation using circularly polarized light microscopy.

Animals↗
PubMed1996

The antinociceptive effect of fluvoxamine.

The authors conducted a study in order to evaluate the antinociceptive effects of the serotonin-selective reuptake inhibitor (SSRI) antidepressant fluvoxamine and its interaction with various opioid receptor subtypes. Male ICR mice were tested with a hotplate analgesia meter. Fluvoxamine elicited antinociceptive effect in a dose-dependent manner following i.p., i.t. and i.c.v. injection. Naloxone 10 mg/kg s.c. did not abolish the fluvoxamine antinociceptive effect. At the next stage fluvoxamine was administered together with various agonists of opioid receptors. When administered together with opiates, fluvoxamine significantly potentiated analgesia at the kappa(3)-opioid receptor subtype (P < .005) and to a lesser extent, at the mu-, delta-, and kappa(1)-opioid receptors. We conclude that fluvoxamine alone induces an antinociceptive effect. This effect is mediated by non-opioid mechanism of action. These results suggest a potential role for fluvoxamine in the management of pain when co-administered with opioids at low doses.

Animals↗
PubMed1996

Predictors of PTSD in injured trauma survivors: a prospective study.

OBJECTIVE: The aim of this study was to prospectively examine the relationship between immediate and short-term responses to a trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: All patients consecutively admitted to a general hospital were screened for the presence of physical injury due to a traumatic event. Fifty-one eligible subjects were assessed 1 week and 6 months after the trauma. The initial assessment included measures of event severity, peritraumatic dissociation, and symptoms of intrusion, avoidance, depression, and anxiety. The follow-up assessments added the PTSD module of the Structured Clinical Interview for DSM-III-R--Non-Patient Version and the civilian trauma version of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder. RESULTS: Thirteen subjects (25.5%) met PTSD diagnostic criteria at follow-up. Subjects who developed PTSD had higher levels of peritraumatic dissociation and more severe depression, anxiety, and intrusive symptoms at the 1-week assessment. Peritraumatic dissociation predicted a diagnosis of PTSD after 6 months over and above the contribution of other variables and explained 29.4% of the variance of PTSD symptom intensity. Initial scores on the Impact of Event Scale predicted PTSD status with 92.3% sensitivity and 34.2% specificity. Symptoms of avoidance that were initially very mild intensified in the subjects who developed PTSD. CONCLUSIONS: Peritraumatic dissociation is strongly associated with the later development of PTSD. Early dissociation and PTSD symptoms can help the clinician identify subjects at higher risk for developing PTSD.

Adult↗
PubMed1996

Bone mineralization as studied by small-angle x-ray scattering.

Small-angle x-ray scattering (SAXS) can provide information on mean size, predominant orientation and typical shape of mineral crystals in bone. In this paper, recent developments of this technique for application in bone research are reviewed. Then the structure of the collagen/mineral composite in bone, as determined by SAXS, is compared for a number of species. The thickness of the mineral crystals was found to increase with age up to a value around 3 to 4 nanometers in adult animals, depending on the species. The SAXS results also suggest the existence of needle-shaped mineral crystals in mouse or rat bone and more plate-shaped crystals in other tissues like adult human bone or mineralized turkey leg tendon.

Animals↗