Pronounced Depression Research Articles

Ocular Effects of α2-Adrenoceptor Activation in Anesthetized Cats

The present study was undertaken to determine the effects of direct administration of the selective alpha 2-adrenoceptor stimulant, B-HT 933, on choroidal blood flow, intraocular pressure and pupil size in anesthetized cats. Anterior segment choroidal blood flow was measured using laser-Doppler flowmetry. B-HT 933 administered by intra-arterial, topical and intracameral routes produced a significant depression of ocular blood flow which was largely abolished by pretreatment with rauwolscine. B-HT 933 did not lower IOP in any of these preparations. The largest doses of B-HT 933 caused a modest mydriasis when given intracamerally. However, this pupillary dilation was not blocked by rauwolscine. These results demonstrate that alpha 2-adrenoceptor activation can produce pronounced depression of anterior segment choroidal blood flow but does not cause a concomitant lowering of IOP or mydriasis in anesthetized cats.

Effects of Halothane and Isoflurane on Collateral Dependent Myocardium in Chronically Instrumented Dogs

The effects of moderate systemic hypotension with halothane (HALO) and isoflurane (ISO) on regional myocardial function and perfusion were studied in dogs with chronic coronary artery occlusion. Vasodilator reserve in collateral-dependent (CD) myocardium was quantified in conscious animals by using a dipyridamole challenge test. Blood flow was distributed homogeneously to the normal (Nl) and CD myocardium at rest, but subendocardial perfusion increased only in the Nl area after dipyridamole. HALO and ISO were administered at doses that reduced diastolic arterial pressure to 50 mm Hg. End-tidal concentrations were 1.3 +/- 0.2 vol% for HALO (1.5 minimum alveolar anesthetic concentration) and 1.8 +/- 0.2 vol% for ISO (1.4 minimum alveolar anesthetic concentration), respectively. Global and regional hemodynamic depression were more pronounced with HALO. Systolic wall-thickening fraction decreased both in the Nl (-37%) and CD area (-27%). Myocardial blood flow to Nl and CD myocardium decreased to a comparable extent. ISO predominantly decreased systemic vascular resistance and, when compared to HALO, decreased systolic wall-thickening fraction less in both the Nl (-19%) and CD area (-18%). In addition, regional myocardial perfusion to both Nl and CD myocardium remained virtually unaltered from conscious control conditions. Despite reductions of diastolic blood pressure to 50 mm Hg, neither HALO nor ISO induced ischemic dysfunction in myocardium with diminished vasodilator reserve. Both anesthetics preserved intercoronary as well as transmural blood flow distribution. During HALO, myocardial perfusion was less both in Nl and CD myocardium due to a more pronounced metabolic depression. We conclude that moderate hypotensive doses of ISO and HALO preserve regional myocardial function of collateral-dependent myocardium in dogs with single vessel occlusion and enhanced collateral circulation.

Effects of Adenosine on Renal Function and Central Hemodynamics After Coronary Artery Bypass Surgery

In the early postoperative period after coronary artery bypass surgery, arterial hypertension commonly occurs which requires intravenous vasodilator therapy. Purine adenosine is a potent vasodilator and when exogenously administered it decreases systemic arterial blood pressure effectively. We evaluated the effects of adenosine on central hemodynamics and renal function when used to control postoperative hypertension after coronary artery bypass grafting (CABG). Two separate series of experiments were performed postoperatively in the Intensive Care Unit (ICU). In the first study (n = 10), postoperative hypertension was controlled in the rewarming phase, with sodium nitroprusside (SNP, 1.7 +/- 0.4 micrograms.kg-1 x min-1) or adenosine (147.2 +/- 38.9 micrograms.kg-1 x min-1) to keep mean arterial systolic pressure at approximately 80 mm Hg. In the second study on a separate group of patients (n = 9), low doses of adenosine (0, 30, 60, 90, and 0 micrograms.kg-1 x min-1) were infused when the patients were normotensive and rewarmed. Central hemodynamics, urine flow (UF), renal blood flow (RBF), glomerular filtration rate (GFR), and ECG were evaluated during periods of 30 min for each drug in the first study and during each dose of adenosine in the second study. RBF and GFR were determined using standard urinary clearance methods for 51Cr-ethylenediaminetetraacetic acid and p-aminohippuric acid. In the first study, adenosine infusion, compared to SNP, decreased (A - V)O2, increased central filling pressures and heart rate, and caused a more pronounced ST segment depression. During adenosine administration RBF (-44%), GFR (-52%), and UF (-76%) decreased, while renal vascular resistance and filtration fraction (FF) were unaltered compared to data obtained during SNP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure and length scales of rotational discontinuities

We have carried out a series of one‐dimensional hybrid (kinetic ions, fluid electrons) simulations, using a nondynamic method to form rotational discontinuities (RDs) at an angle of θBn = 60° between the normal direction and the upstream magnetic field. Ion kinetic effects are found to be important concerning the stability of the current layer, its thickness and scaling, and its dependence on initial conditions. When the ions are initialized with transverse velocities derived from Hall MHD, RDs with both senses of rotation α1 = ±180° can be stable down to widths of a few c/ωpi, (ion inertial lengths). This initialization gives reliable results except in the case of thin electron‐sense RDs with a rotation angle α1 = −180°, which have a pronounced depression of the transverse ion velocity, and develop more easily starting from a nonrotational transition of the ion flow. At a plasma beta of order unity, there is a minimum width of a few c/ωpi for transitions of both senses of rotation. Thin RDs show a significant upstream heat flux and temperature anisotropies. Their small‐scale structure is embedded in a larger envelope of the order of 100 c/ωpi. In a cold plasma, ion‐sense RDs with α1 = 180° have a minimum width which scales with the ion inertial length. In a warm plasma, the thickness increases with the square root of the ion beta due to the finite ion Larmor radius. There appear to be no stationary structures for rotation angles |α1| significantly larger than 180°. However, the associated breakup time increases with the initial thickness, eventually approaching the stable MHD limit for transitions very wide compared to the ion Larmor radius. The two senses of rotation α1 = ±270° show completely different mechanisms for disintegration. Electron‐sense rotations appear to be composed of a stable, large amplitude α1 = −360° solitary wave at the upstream edge and an ion sense α1 = 90° rotation; a slight difference in speed separates the α1 = −270° total rotation over time. Ion‐sense RDs with α1 = 270° are metastable: their current structure disintegrates explosively after an initial stable interval (many 100 Ωci−1 for wide transitions, where Ωci is the ion cyclotron frequency), when internal ion heating has increased the average gyroradius above the width of the transition.

The Tectonics of Tachira: Insight into North Andean Deformation

Tachira forms the connecting link between the Merida Andes of Venezuela, and Cordillera Oriental of Colombia, and the Santander massifs. On the basis of surface mapping and subsurface data, its structural style and kinematics are discussed. Tachira is a pronounced structural depression relative to the Andean branches it connects. It comprises a bewildering network of structures, containing all the elements of the surrounding Andean branches. The structural relief as well as the adjacent foredeep were mainly formed during Neogene deformation. The Tachira depression is composed of a system of southwestward plunging inverted Early Cretaceous troughs and a tectonic block mosaic, with mostly transpressive block boundaries; dextral for the northeast-trending, sinistral for the southeast-trending zones of motion. The complex combinations of folding and thrusting with steep faults in transpressive zones are interpreted as [open quotes]flower structures.[close quotes] The structural pattern is supplemented by the more purely compressive north-south trends, revealing large-scale thrusting and disharmonic fault-bend folding, and by east-west trending transfer zones of dextral shear. Uplift of the Cordillera Oriental against the Tachira depression was established by movement in a sinistral transpressive zone (Bramon fault), coupled with thrusting towards the Llanos foredeep. The structural patterns of the Tachira depression fit amore » kinematic scheme of east-west compression. The compressional shortening, apparently not exceeding 10 km, and 60 km of distributed strike-slip movement, similar to the displacement along the Bocono fault at the northeast end of the Merida Andes, appears compatible with the Neogene block movement of northern South America.« less

Myofibrillar fatigue versus failure of activation during repetitive stimulation of frog muscle fibres.

1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature, 2-5 degrees C; sarcomere length, 2.10 microns) were fatigued using two separate protocols that led to different degrees of depression of tetanic force. Under control conditions the fibre was stimulated to produce a 1 s fused isometric tetanus at 300 s intervals. A moderate degree of fatigue (tetanic force reduced to 70-80% of the control value) was produced by decreasing the intervals between tetani to 15 s ('fatiguing protocol 1'). A more pronounced depression of tetanic force (to 40-50% of the control value) was produced by evoking a single twitch at 1-2 s intervals ('fatiguing protocol 2'). 2. Fatiguing protocol 1 reduced the contracture response to submaximal and supramaximal concentrations of caffeine (3-15 mM) in proportion to the decrease in tetanic force. These results support the view that fatiguing stimulation according to protocol 1 leads to a true 'myofibrillar fatigue' with no failure of activation of the muscle fibre. 3. Fatiguing protocol 2 reduced the amplitudes of isometric twitch and tetanus to below 10 and 50% of the control values, respectively. By contrast, the maximal contracture response to caffeine (15 mM) was depressed by merely 2-3% of its prefatigue value. 4. Force and instantaneous fibre stiffness were recorded simultaneously during twitch and tetanus as fatigue was induced by protocol 2. During the initial part of fatigue (tetanic force reduced by 25% of control) stiffness was reduced by merely 9% in accordance with previous measurements during fatigue induced by protocol 1. However, with further depression of twitch and tetanus by protocol 2 there was a marked reduction of fibre stiffness. These results, together with the findings reported under point 3, strongly suggest that at an advanced state of fatigue induced by protocol 2 the decrease in active force is largely due to failure of activation of the contractile system. 5. Muscle fibres were quickly frozen for electron microscopical examination after shortening below slack length (to approximately 1.6 microns sarcomere spacing) during tetanic stimulation. In non-fatigued fibres, and in fibres fatigued according to protocol 1, the myofibrils exhibited a straight appearance throughout the preparation suggesting that the entire volume of the fibre was properly activated. In fibres fatigued by protocol 2, on the other hand, only the most peripheral layers of myofibrils remained straight after shortening, whereas the centre of the fibre showed marked waviness indicating failure of the inward spread of activation in this case.

The global behavior of the March 1989 ionospheric storm

By any measure the magnetic storm beginning with a sudden storm commencement at 0128 UT March 13, 1989 must be classified historically as a great storm. Associated with this great magnetic storm was the drastic modification of the normal ionosphere lasting for several days. To study this abnormal behavior, ionospheric data collected at 52 ionosonde stations and 12 total electron content observing stations have been analyzed. The global data show a longitudinal dependence on the storm behavior; a pronounced worldwide depression in the diurnal maximum values of f0F2; the extreme depression of the diurnal-minimum in f0F2 to a frequency less than 2 MHz at many stations, sometimes accompanied by an unprecedented rise in h'F to 700 km or more; the presence of traveling ionospheric disturbances; the presence of large-scale standing oscillations; the development of hemispheric asymmetry; and the suppression of the equatorial anomaly. These and other unusual phenomena are described in this paper.

Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans.

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)

CEREBRAL RESPONSES IN HORSES TO HALOTHANE AND ISOFLURANE ANAESTHESIA: EEG POWER SPECTRUM ANALYSIS AND DIFFERENCES IN ARTERIOVENOUS OXYGEN CONTENT

In a prospective study we compared the EEG variables total amplitude (TA), 80% spectral edge frequency (SEF-80), the ratio of fractional amplitudes distributed into the BETA and DELTA frequency band (BETA/DELTA-ratio), and differences in arteriovenous oxygen content (AVD02), obtained from horses anaesthetized with either halothane (H; n=4) or isoflurane (I; n=4) in oxygen. All horses underwent orthopaedic procedures. After premedication with xylazine (0.88 mg/kg IV), anaesthesia was induced with diazepam (0.033 mg/kg IV) and ketamine (2.2 mg/kg IV). During anaesthesia horses were ventilated using IPPV. EEG variables and AVD02 were recorded at equal levels of surgical anaesthesia (stage III/1–2), as determined by clinical signs and a dominant delta activity in the EEG power spectrum. PaC02was kept between 35 mmHg and 45 mmHg, PaO2above 100 mmHg, and mean arterial blood pressure (MAP) was adjusted to at least 80 mmHg. The average body temperature was 35.4 ± 1.1°C (H) and 35.6 ± 0.7°C (I), respectively. In horses anaesthetized with I, TA was significantly higher (P<01) (I: 3533 ± 70 γV; H: 235.9 ± 63.4 γV), whereas SEF-80 (I: 10.7 ± 0.7 Hz; H: 12.4 ± 0.7 Hz) and BETA/DELTA-ratio (I: 035 ± 0.06; H: 0.53 ± 0.12) were significantly lower (P<01) compared with H. We also observed significantly lower (P<05) AVD02 values with I (1.5 ± 0.5 Vol%) than with H (2.0 ± 1.2 Vol%). Since a depression in cerebral activity during anaesthesia is characterized by a decrease in EEG frequency content and a concomitant increase in EEG amplitude, the authors conclude that at equal levels of surgical anaesthesia, isoflurane exerts a more pronounced depression in cerebral electrical and metabolic activity in horses.

Theoretical analysis of Ei ⊗ eα ↔ Ej ⊗ eα vibronic Jahn-Teller spectra

The theoretical investigation of optical vibronic Jahn-Teller spectra of E i ⊗ e α ↔ E j ⊗ e α electronic transitions reveals intriguing features. Notably, perpendicular and also parallel cold allowed intensity may develop along the pertinent Jahn-Teller (J-T) progressions: 0(± 1 2 ) → v(⊣ 1 2 , ± 3 2 ) , and 0(± 1 2 ) → v(± 1 2 ) , respectively, exhibiting quite different, unique intensity patterns. Contributions of intensities from both polarizations result in interesting J-T superposition intensity patterns. Spectra will not change on simultaneously reversing the direction of J-T distortion (displacement) in both electronic states involved in the transition. Remarkably this behavior still holds for perpendicular intensity on reversing the direction of J-T distortion in one of the electronic states only. Quite surprisingly, parallel intensity patterns will be affected drastically upon such reversal, thus enabling one to determine whether a change in the direction of J-T distortion takes place upon electronic transition. For no change in J-T distortion upon electronic transition the J-T vibronic structure of perpendicular cold allowed intensity may be well developed, whereas that of parallel cold allowed intensity degenerates into the vibrationless transition, thus disclosing no evidence for the occurrence of J-T activity. A mere reversal of J-T distortion during the radiative process may lead to a well developed J-T progression carrying parallel cold allowed intensity. The cold allowed perpendicular vibronic structure associated with each of the two relevant J-T progressions may simultaneously develop two great maxima with a pronounced depression between them exhibiting complete intensity cancellation which may grow into a wide “spectroscopic desert”. This dramatic phenomenon may give the impression of the occurrence of two completely separate electronic transitions in the spectrum.

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

The induction of the activity of cerebral ornithine decarboxylase (EC 4.1.1.17) and mRNA by electrical stimulation exhibits regional differences. The effects of the enzyme inhibitor difluoromethylornithine on these regional variations was examined. Administration of this inhibitor resulted in pronounced depression of both basal and induced activity of ornithine decarboxylase in the hippocampus. Basal activity of the enzyme in the neocortex and the cerebellum appeared to be resistant to difluoromethylornithine but the induced enzyme activity was sensitive to the effects of this inhibitor. Susceptibility to difluoromethylornithine may be directly correlated with a slower turnover rate for ornithine decarboxylase. These results suggest that ornithine decarboxylase in the hippocampus may possess a longer half-life than its counterparts in other regions of the brain. Pretreatment with difluoromethylornithine had no effect on the induced ornithine decarboxylase mRNA in the neocortex. Thus, elevated activity of ornithine decarboxylase enzyme, due to electrical stimulation, appears to not have any effect on either the transcription or the decay rate of the induced ornithine decarboxylase mRNA. These findings support the concept of region-specific regulation of cerebral ornithine decarboxylase.

GABA A receptors modulate axonal conduction in dorsal columns of neonatal rat spinal cord

γ-Aminobutyric acid (GABA) can influence conduction in a number of axonal preparations from the peripheral and central nervous system. In the spinal cord, the excitability of primary afferent terminals has long been known to be affected by GABA. Whether conduction in the long fiber tracts of the spinal cord can be similarly modulated is unknown. Since GABA causes a pronounced depression of excitability in preparations of unmyelinated axons, and myelination is incomplete in the neonatal rat, we tested whether GABA can modulate conduction in the dorsal columns of 10–17-day-old rats. Experiments were performed in vitro, on isolated dorsal column segments (n = 18). The extracellular compound action potential evoked by submaximal stimuli was recorded with a glass micropipette positioned 0.5–2.0 mm from a stimulating electrode. At concentrations of 10 −4−10 −3 M, GABA decreased excitability, reversibly depressing the compound action potential amplitude, and increasing the latency by47 ± 11%and22 ± 9% (mean±S.E.M., n = 5, 10 −3M), respectively. These effects were blocked by picrotoxin and mimicked by isoguvacine (10 −4 M), which decreased the compound action potential amplitude by44 ± 10% and increased the latency by9 ± 4% (n = 5). Lower concentrations of these agents caused a modest increase in excitability. At 10 −5 M, GABA increased the compound action potential amplitude by14 ± 2% and decreased the latency by3 ± 2% (n = 5). Our results demonstrate that functional GABA A receptors are present in neonatal dorsal columns. While the physiologic role of these receptors is not yet clear, these data suggest that axonal conduction in long tracts of the spinal cord may be subject to modulation by extrasynaptic mechanisms.

Miscibility of poly(methoxymethyl methacrylate) and poly(methylthiomethyl methacrylate) with poly(vinylidene fluoride)

The miscibility behaviour of poly(methoxymethyl methacrylate) (PMOMA) and poly(methylthiomethyl methacrylate) (PMTMA) with poly(vinylidene fluoride) (PVDF) was examined by differential scanning calorimetry. PMOMA/PVDF blend system was judged to be miscible on the bases of the presence of a single, composition-dependent glass transition for the blend and a pronounced melting point depression of the PVDF component. Furthermore, lower critical solution temperature (LCST) behaviour was observed for all PMOMA/PVDF blends. PMTMA/PVDF blends were found to be immiscible. Based on the melting point depression of PVDF in PMOMA/PVDF blends, the interaction parameter B was found to be -14.5 J/cm3.

Relation of plasma thyroxine binding to thyroidal activity and determination of thyroxine binding proteins in a turtle, Pseudemys scripta

The ability of plasma to bind thyroxine (T 4) was examined in the turtle, Pseudemys scripta, in relation to variations in thyroidal state associated with age, sex, environment, and surgical and chemical manipulations. Relative plasma binding activity was assessed by use of binding to [ 125I]T 4 on minicolumns of Sephadex G-25 (fine). Hypothyroidism induced by surgical thyroidectomy (Tx) or goitrogen (Methimazole) treatment resulted in a marked depression of plasma binding (50- to 100-fold) in juveniles, and T 4 treatment restored binding after 4–6 weeks in long-term Tx animals and increased levels in intact animals. Among intact turtles or those made slightly hypothyroid by partial thyroidectomy, binding was consistently correlated with plasma T 4. For example, juvenile turtles kept under continuous light and constant temperature (28°) for 4.5 months showed a pronounced depression of plasma T 4 (2.6 ± 1.1 ng/ml) and binding capacity compared to animals raised under variable conditions (T 4 = 69.6 ± 22 ng/ml) for the last 2 months. Plasma T 3 was < 1 ng/ml in all cases. Binding levels in adult turtles were similar to juveniles, but females had significantly higher binding levels than males which paralleled differences in their plasma T 4 (137 ± 17.4 vs 83.9 ± 13.8 ng/ml). These variations in binding were independent of total plasma protein and albumin. Plasma T 4 binding measured on Sephadex G-25 was reversible and reduced by addition of exogenous T 4. The affinity for T 3 was 10- to 100-fold less than for T 4. When plasma preincubated with [ 125I]T 4 was electrophoresed on polyacrylamide slab gels (7% nonreducing) only a small percentage of radiolabel was associated with albumin and the majority with a slower migrating protein(s). Addition of unlabeled T 4 displaced binding from the slower migrating region to the albumin and dye front (unbound). In contrast, plasma from Tx turtles showed only minimal binding and radiolabel was associated primarily with the albumin fraction. Elution of proteins from gels confirmed that only the slower migrating components bound T 4 when tested on Sephadex G-25, and Tx animals lacked this binding component. The protein(s) responsible for most of the T 4 binding appears to exist in low concentration. Limited comparative studies with human blood showed a similar binding activity on Sephadex G-25, but electrophoretic mobilities of binding proteins were distinct from those in the turtle. Evidence suggests that this binding protein is not prealbumin. Thus, contrary to prevailing views for ectotherms, the levels of total plasma T 4 in this turtle are higher than those typical of mammals and the turtle may possess a unique T 4 binding protein that is functionally analogous to thyroxine binding globulins in mammals.

Anaesthetic suppression of transmitter actions in neocortex

1. The effects of general anaesthetics were investigated on neuronal sensitivities to transmitter substances, which were determined by iontophoretic applications of acetylcholine, glutamate, N-methyl-D-aspartate (NMDA) and gamma-aminobutyrate (GABA) during intracellular recording in in vitro slice preparations of neocortex (guinea-pig). 2. In most of the 65 neurones studied, perfusion of isoflurane (0.5-2.5 minimum alveolar concentration (MAC)) or Althesin (25-200 microM) and, in some cases, halothane (0.5-2 MAC), markedly reduced the depolarizing responses and associated membrane conductance changes evoked by dendritic applications of acetylcholine, glutamate, NMDA and GABA. 3. The order of depression was acetylcholine greater than glutamate or NMDA much greater than GABA. This selectivity could also be assessed from the EC50 for the isoflurane-induced depression of the just-maximal responses to acetylcholine, which was 0.9 MAC compared with an EC50 = 1.9 MAC for the suppression of glutamate responses. The selectivity was less pronounced in the case of the actions of Althesin, where the EC50s were 75 microM for the depression of acetylcholine responses and 90 microM for the depression of glutamate responses. 4. The hyperpolarizing responses observed when GABA was applied near the perikaryon in 7 neurones, were slightly reduced (approximately 15%) in 4, and unchanged in 3 neurones during anaesthetic application. 5. The pronounced depression of the responsiveness to the putative arousal transmitters and an observed blockade of acetylcholine-induced potentiation of glutamate actions suggest that anaesthetics produce unconsciousness, at least in part, by interfering with subsynaptic mechanisms of neocortical activation.

Fish oil dietary supplementation reduces Ia expresion in rat and mouse peritoneal macrophages

Preliminary studies suggest that administration of fish oil fatty acids may be beneficial in several immunological diseases; therefore, we studied the effect of fish oil dietary supplementation on the expression of Ia in stimulated murine peritoneal macrophages. Rats ( n = 19) and mice ( n = 27) on standard rodent feeding were separated in experimental (E) and control (C) groups that received fish oil or saline solution, respectively, daily for 4 weeks by esophageal gavage. Cholesterol serum levels were significantly lowered by fish oil (E vs C, P < 0.01). E and C groups were injected intraperitoneally with Listeria monocytogenes (LM) and peritoneal cells were harvested 4 and 7 days after infection. Decreased expression of Ia induced by LM was found in rats (C = 49.68 ± 5.09%, E = 16.95 ± 4.3%, P < 0.01) and mice (C = 47.38 ± 7.63%, E = 26.66 ± 1.92%, P < 0.01). Animals with a more pronounced depression of serum cholesterol (reduction of 44.04 ± 1.52% of baseline levels) had more depression of Ia expression (6.47 ± 1.22%, P < 0.001 vs control). Reduction of Ia expression was not related to PGE 2 production by peritoneal cells. Reduction of Ia expression by fish oil could induce down-regulation of antigen presentation and alloreactivity.

In vitro translational activity of messenger-RNA isolated from mice treated with the interferon inducer, polyriboinosinic acid·polyribocytidylic acid

Treatment of mice with interferon and interferon inducers causes down regulation of a number of hepatic proteins. In a previous publication it was demonstrated that these treatments depress hepatic protein synthesis and increase protein degradation, particularly of the endoplasmic reticulum Gooderham NJ and Mannering GJ, Arch Biochem Biophys 250: 418–425, 1986. In the present study the effects of polyriboinosinic acid-polyribocytidylic acid (poly IC) treatment on mouse hepatic RNA levels and the translation of this RNA in a cell-free system were examined. Poly IC treatment of mice increased hepatic poly (A +)RNA levels. The translation of isolated poly(A +)RNA was evaluated at various intervals after the administration of poly IC. Translation was marginally increased at 3–6 hr after treatment and depressed after 12–18 hr. Antibodies were employed to examine the effects of poly IC treatment on specific polypeptides in order to evaluate the in vitro translation of mRNAs for tyrosine aminotransferase and albumin; translation of these proteins was biphasic with pronounced depression. These studies indicate that in vivo interferon may regulate gene expression by altering levels of hepatic proteins via increased transcription and decreased translation.

Mechanism of cocaine-induced myocardial depression in dogs.

Cocaine causes pronounced depression of left ventricular function in conscious dogs immediately after intravenous administration. To examine this effect, 14 mongrel dogs were anesthetized with pentobarbital sodium (32 mg/kg) and instrumented with arterial and venous catheters and a Doppler blood flow transducer on the left circumflex coronary artery. Two weeks later, heart rate, blood pressure, coronary blood flow, and regional left ventricular ejection fraction (by two-dimensional echocardiography) were measured before and 1, 2, 5, and 10 minutes after cocaine (4 mg/kg i.v.), while the animals were fully conscious. Heart rate, blood pressure, and coronary blood flow were increased significantly at each time after cocaine. Regional ejection fraction, however, was depressed by 50 +/- 7%, 35 +/- 4%, and 21 +/- 4% at 1, 2, and 5 minutes after cocaine treatment, respectively. Ten minutes after cocaine treatment, regional ejection fraction had recovered to a level not significantly different from baseline. Because the observed myocardial depression after cocaine was accompanied by a large increase in the rate-pressure product, and presumably, myocardial oxygen consumption, this depression could have been secondary to increased myocardial oxygen demand not appropriately matched by an increase in coronary blood flow. To minimize the effects of cocaine on myocardial oxygen demand, a subset of six dogs received cocaine (4 mg/kg i.v.) while sedated with pentobarbital (25 mg/kg). In these dogs, cocaine did not significantly alter heart rate or blood pressure; however, regional ejection fraction was significantly depressed by 44 +/- 5% and 36 +/- 6% at 1 and 2 minutes after cocaine treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Ninety-day inhalation study in rats, comparing smoke from cigarettes that heat tobacco with those that burn tobacco

Eight groups of 30 male and 30 female rats were exposed 1 hr per day, 5 days per week for 13 weeks, to smoke from reference (tobacco burned) or test (tobacco only heated) cigarettes, at nicotine concentrations of 5, 15, or 30 μg/liter of air. Similar smoke concentrations of wet total particulate matter and carbon monoxide were produced in each of the test/reference comparisons. There was a pronounced depression of minute ventilation of animals in the reference groups, but not in the test animals. Blood carboxyhemoglobin concentrations were similar in animals exposed to smoke from test and reference cigarettes. Plasma concentrations of nicotine and cotinine in the test groups were higher than in the reference groups. There were no differences between the smoke-exposed groups in terms of body weight or feed consumption. At necropsy, an increase in heart weight was noted in both high exposure groups. There were notable differences in histopathology, with fewer and less-pronounced changes in the test groups than in the reference groups. Many of the histopathological responses induced in the reference groups were absent in the test groups. Overall, the study demonstrated a substantial reduction in the biological activity of smoke from the test cigarette when compared with the reference.

Experimental autoimmune thyroiditis in mice chronically treated from birth with anti-IgM antibodies

The role of T lymphocytes in the pathogenesis of experimental autoimmune thyroiditis in mice is well established while the role of B lymphocytes is unclear. Mice with thyroid lesions have thyroglobulin antibodies whereas these antibodies can occur in mice immunized with Tg that do not develop thyroid lesions. To determine whether thyroglobulin antibodies are necessary for the development of the thyroid infiltrates with mononuclear cells, which are characteristic for experimental autoimmune thyroiditis, AKR mice chronically treated from birth with goat anti-mouse IgM antibodies were immunized with mouse thyroglobulin in Freund's complete adjuvant when they were 7 weeks old. Control mice, similarly immunized, were chronically injected from birth with normal goat γ-globulin. Three weeks after immunization, all mice were sacrificed, thyroglobulin antibodies in the serum were measured by hemagglutination assay and enzyme-linked immunosorbent assay, and thyroid pathology was assessed. The serum concentration of IgG and IgM, the percentage of B and T lymphocytes in the spleen (flow cytometry), and the in vitro proliferative response of spleen lymphocytes to stimulation by PHA, LPS, and Tg were also measured. All mice treated with anti-IgM antibodies did not have detectable thyroglobulin antibodies but 63% of these mice and 88% of control mice (all of which had thyroglobulin antibodies) had thyroid lesions. Mice treated with anti-IgM antibodies that did not have thyroid lesions had a more pronounced depression of B lymphocytes than similarly treated mice that had thyroid lesions. These experiments suggest that thyroglobulin antibodies are not necessary for the development of thyroid infiltrates with mononuclear cells. B lymphocytes could still participate in the production of experimental autoimmune thyroiditis by presenting thyroglobulin to helper T lymphocytes.