Sleep to forget: interference of fear memories during sleep.

Memories are consolidated and strengthened during sleep. Here we show that memories can also be weakened during sleep. We used a fear-conditioning paradigm in mice to condition footshock to an odor (conditioned stimulus (CS)). Twenty-four hours later, presentation of the CS odor during sleep resulted in an enhanced fear response when tested during subsequent wake. However, if the re-exposure of the CS odor during sleep was preceded by bilateral microinjections of a protein synthesis inhibitor into the basolateral amygdala, the subsequent fear response was attenuated. These findings demonstrate that specific fear memories can be selectively reactivated and either strengthened or attenuated during sleep, suggesting the potential for developing sleep therapies for emotional disorders.

Activity-dependent layer-specific changes in the extracellular chloride concentration and chloride driving force in the rat hippocampus.

The transmembrane distribution of chloride anions (Cl⁻) determines the direction of the Cl⁻ flux through GABA(A) receptors; this establishes whether GABA(A) receptor-mediated responses are hyperpolarizing or depolarizing in neurons. Thus an activity-dependent reduction in the efficacy of inhibitory responses can be the result of an activity-induced reduction of the Cl⁻ driving force. Using Cl(-)-sensitive electrodes, we measured the extracellular Cl⁻ concentration ([Cl⁻](o)) in each layer of the hippocampus under control conditions and after stimulation. In the control condition, [Cl⁻](o) was lower within the CA1 region (112.9 ± 1.3 mM; mean ± SD) than the CA3/dentate gyrus areas (117.7 ± 1.2 mM). Stimulation of CA3 pyramidal cells led to an increase in the [Cl⁻](o). The maximum values were observed in the stratum lacunosum-moleculare (253.4 ± 51.1 mM) and in the hilus (261 ± 43.7 mM), whereas in the granular cell layer, it reached only 159.5 ± 41 mM. The stimulation-induced [Cl⁻](o) increase was followed by a period of decreasing [Cl⁻](o) that fell below the control values. The maximum undershoot (21.6 ± 0.7 mM) was observed in the s. radiatum. Systemic application of the gap junction blocker carbenoxolone significantly decreased the stimulation-induced Cl⁻ extrusion in the dentate gyrus but only slightly modified it in the CA1 area. Carbenoxolone also drastically reduced the Cl⁻ clearance. The time constant of the Cl⁻ clearance was similar between layers (83.4 ± 15.9 ms) but increased after carbenoxolone application (207.1 ± 44.4 ms). Stimulation-induced changes in the [Cl⁻](o) significantly decreased the Cl⁻ driving force and resulted in large fluctuations between layers (Δ = 9.4 mV). The lowest value was observed in the stratum radiatum of the CA1 and the hilar region (7.7 mV), whereas the highest value was calculated for the granule cell layer (16.3 mV). We suggest that a decrease of the extracellular space is mainly responsible for the rapid [Cl⁻](o) increase while the gap junction coupled astrocytic network plays a key role in the activity-dependent redistribution and clearance of Cl⁻ across layers of the hippocampus.

The effect of propranolol on blood viscosity changes induced by experimental coronary occlusion.

The effect of propranolol treatment was investigated in the myocardial ischemia-induced hyperviscosity state in anesthetized dogs. In untreated control dogs, low shear blood viscosity rose progressively, following an acute occlusion of the left anterior descending coronary artery; this effect was partially but significantly reduced by intravenously administered propranolol (0.2 mg/kg). The effect of the in vitro addition of propranolol was also determined upon viscosity of blood samples obtained at hourly intervals from dogs subjected to similar coronary ligation. The in vitro addition of propranolol did not produce a similar reversal of the hyperviscosity state observed in the blood obtained from dogs after coronary ligation.

Use of antibiotics in dental practice.

Penicillin G administered parenterally or penicillin V administered orally are currently the antibiotics of choice for treatment of dental infections of usual etiology. Infections caused by penicillinase-producing staphylococci or those involving gram-negative bacteria should be treated with a penicillinase-resistant penicillin or an ampicillin-like derivative, respectively. Erythromycin is a second-choice bacteriostatic antibiotic, becoming first choice for treating dental infections in patients allergic to penicillin. The cephalosporins, similar in action to ampicillin-like penicillin derivatives, may be used with caution in patients who have exhibited delayed-type allergic reactions to penicillin and when erythromycin cannot be used. Their lack of advantage over other agents, and their cost, precludes routine use for usual dental infections. Clindamycin administered orally or lincomycin administered parenterally are reserve antibiotics indicated for treatment of bone infections and/or anaerobic infections refractory to commonly used antibiotics. Tetracyclines are, at best, third-choice agents for usual dental infections. However, they are useful for cases of acute necrotizing ulcerative gingivitis requiring systemic antibiotic therapy when penicillin is precluded. Vancomycin and streptomycin are used prophylactically for prevention of infective endocarditis in patients with prosthetic heart valves. Nystatin remains a first-choice agent for treatment of oral candidal infections. Ketoconazole, an orally active systemic antifungal agent, may be used for monilial infections of the oral cavity refractory to nystatin. Chemotherapy of viral infections is difficult because of the timing of events of the disease process versus appearance of clinical symptoms and lack of effective agents with selective toxicity. Herpes infections of the oral cavity have been treated--with limited success--with idoxuridine. Acyclovir, a newer antiviral drug, offers little clinical benefit for herpes infections in usually healthy patients but may be of value for treating such infections in immunocompromised patients. All antimicrobial agents may cause adverse reactions of varying degrees of severity. Most orally administered antibiotics may cause gastrointestinal disturbances. Superinfections occur with broad-spectrum antibiotics and a severe form of superinfection, antibiotic-associated colitis, has occurred with almost all antibiotics. Allergic reactions of all degrees of severity can occur with most antibiotics. The penicillins, followed by the cephalosporins and tetracyclines, are most frequently implicated in these reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Principles of anti-infective therapy.

Antimicrobial drugs, along with competent surgical procedures, provide an effective means for restoration of oral health. In dentistry, antibiotics are indicated for either treatment of acute infections or for prophylactic coverage of patients at risk for developing bacterial endocarditis or other infections as the result of bacteremia caused by dental procedures. Whenever possible, a bactericidal agent is preferred because of greater effectiveness and less reliance on host defense mechanisms. For maximal effectiveness of antibiotic therapy of orodental infections, several factors must be evaluated in choosing an antibiotic: (1) antibacterial spectrum and specificity of the agent; (2) degree of bacterial resistance reported for the antibiotic; (3) concentrations achieved at various sites; (4) age, type, and extent of infection; and (5) various host factors.

Early deleterious hemorheologic changes following acute experimental coronary occlusion and salutary antihyperviscosity effect of hemodilution with stroma-free hemoglobin.

Viscometric measurements were made on the blood of anesthetized dogs before and following acute occlusion of the left anterior descending coronary artery. Within an hour of the occlusion, the low-shear viscosity of whole blood was significantly increased and continued to rise thereafter. This was accompanied by significant increments in the yield-shear stress of whole blood, suggesting accelerated tendencies in aggregation and plasma viscosity. In another group of dogs, 1 hour after coronary occlusion, rapid isovolemic hemodilution was performed with an 8% solution of stroma-free hemoglobin, reducing the hematocrit to 24%. This was followed by marked reduction of whole blood viscosity at all shear rates, abolition of the yield-shear stress, and reduction of plasma viscosity. These findings suggest that a hyperviscosity state develops early in acute myocardial ischemia which is detrimental to collateral perfusion of the marginal zone of ischemic myocardium. Such hyperviscosity syndrome can be blocked by hemodilution with stroma-free hemoglobin.

The effect of hemodilution with stroma-free hemoglobin and dextran on collateral perfusion of ischemic myocardium in the dog.

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.

Myocardial blood flow and O2-supply following dextran-haemodilution and methaemoglobinaemia in the dog.

The adequacy of oxygen-supply to the left ventricular myocardium was compared in anaesthetised dogs following: a) isovolaemic haemodilution with Dextran 70 (to haematocrit = 20 +/- 2%), b) the acute induction of methaemoglobinaemia (to methaemoglobin-concentration = 53 +/- 7%), bu subjecting them to an exchange-transfusion with methaemoglobin-containing erythrocytes in dextran) and c) a control exchange-transfusion with normal homologous erythrocytes in dextran. Myocardial oxygen-supply was assessed by the measurement of myocardial blood flow (using 15 +/- 5 micron microspheres) and of the PO2 in coronary sinus blood. In dextran-haemodiluted dogs, mean myocardial blood flow was 92% greater than in the control group, allowing the maintenance of normal coronary sinus PO2. In the methaemoglobinaemic group, flow was only 15% greater than in the control group; because oxygen-capacity was halved in this group, myocardial oxygen supply was impaired and coronary sinus PO2 fell. Infusions of isoproterenol (0.1 microgram . kg-1 . min-1) produced similar myocardial flow-increments in the haemodiluted and control groups with similar transmural distribution. In the methaemoglobinaemic group, however, the subendocardial flow-increment was reduced, in association with a further reduction in coronary sinus PO2 and an attenuated contractile response to the drug. These findings suggest that the rheological effects of haemodilution play an important role in the maintenance of myocardial oxygen-supply, but in significant methaemoglobinaemia, the oxygen supply of the myocardium may be severely curtailed.

Actions of morphine on the segmental reflex of the decerebrate-spinal cat.

1. The actions of morphine were studied on the segmental reflex of the decerebrate-spinal cat. Morphine decreased arterial blood pressure.2. Morphine inhibited mono- and polysynaptic reflexes. The influence of morphine on monosynaptic reflexes was more obvious at stimulation of the dorsal root at a frequency of 12.5 Hz than at 0.5 or 2.5 Hz.3. The total amount of activity recorded from the ventral root after morphine depended on whether or not the evoked reflex was maximal or submaximal.4. These actions of morphine were antagonized by naloxone.