Low-lying, Rydberg states of polycyclic aromatic hydrocarbons (PAHs) and cyclic alkanes.

TD-DFT calculations of low-lying, Rydberg states of a series of polycyclic hydrocarbons and cyclic alkanes are presented. Systematic variations in binding energies and photoelectron angular distributions for the first members of the s, p and d Rydberg series are predicted for increasing molecular complexity. Calculated binding energies are found to be in very good agreement with literature values where they exist for comparison. Experimental angle-resolved photoelectron spectroscopy results are presented for coronene, again showing very good agreement with theoretical predictions of binding energies and also for photoelectron angular distributions. The Dyson orbitals for the small "hollow" carbon structures, cubane, adamantane and dodecahedrane, are shown to have close similarities to atomic s, p and d orbitals, similar to the superatom molecular orbitals (SAMOs) reported for fullerenes, indicating that these low-lying, diffuse states are not restricted to π-conjugated molecules.

Anisotropic hot electron emission from fullerenes.

Photoelectron spectra for fullerenes C(60) and C(70) ionized using 800 nm laser pulses with pulse durations from 120 to 1000 fs show thermal electron kinetic energy distributions but they also exhibit angular anisotropy with respect to the laser light polarization. The effective temperature of electrons, measured along the laser polarization direction, is significantly higher than in the perpendicular direction. We explain this observation by considering that the emission of the thermal electrons is uncorrelated with the phase of the laser pulse, unlike directly ionized electrons, and, depending on the time of emission, they may experience an additional "kick" from the vector potential of the laser field when they are emitted from the molecule.

Directly probing spin dynamics in a molecular magnet with femtosecond time-resolution.

We show that a vanadium-chromium Prussian blue analogue, which is a room-temperature molecule-based magnet, displays a fast magnetic response on a femtosecond timescale that is attributed to the super-exchange interaction between the metal ions. These dynamics are obtained from femtosecond Faraday magneto-optical (MO) measurements, performed at 50 and 300 K. Exciting at the ligand-to-metal charge-transfer (LMCT) band results in the formation of the 2E excited state on the Cr ion via intersystem crossing (ISC) from the 4LMCT state in less than 250 fs. Subsequent vibrational relaxation in the 2E state occurs on a 0.78 ± 0.05 ps timescale at 50 K and 1.1 ± 0.1 ps at 300 K. The MO measurements can detect the formation of the 2E state on the Cr ion from the change in the super-exchange interaction taking place as a result of the corresponding spin flip associated with the formation of the 2E state. These results open up a new avenue to study molecular magnets using a powerful method that is capable of directly probing spin dynamics on a sub-picosecond timescale in thin film environments.

Diurnal variations in twenty-four-hour energy expenditure during growth hormone treatment of adults with pituitary deficiency.

The effects of growth hormone (GH) treatment on 24-h energy expenditure (EE) were studied in a open trial over a period of 4 weeks. Five subjects, four men and one woman, with a history of complete GH deficiency were included. All the subjects were examined on 2 consecutive days on baseline and, thereafter, at six occasions during a period of 1 month (days 1, 2, 5, 8, 15, and 30). The dose of GH was 0.25 U/kg.week, administered sc once a day in the evening. EE was determined in a chamber for indirect calorimetry. Body composition was determined with dual-energy x-ray absorptiometry and computed tomography using a four-scan technique. Blood samples were examined using well-established RIAs. During the first 2 weeks, 24-h EE increased by 6 +/- 3% (range 1-8%) from 40.9 +/- 4.8 to 42.9 +/- 4.8 kcal/24 h.kg (P < 0.05), sleeping metabolic rate by 14 +/- 3% (range 10-18%) from 28.4 +/- 1.9 to 32.9 +/- 2.2 kcal/24h.kg (P < 0.001), and basal metabolic rate by 11 +/- 7% (range 0-18%) from 29.6 +/- 2.4 to 33.3 +/- 2.6 kcal/24h.kg (P < 0.05). No change was found in daytime EE. The increase in EE covaried with changes in insulin-like growth factor 1, the free T3/free T4 ratio, insulin-like growth factor-binding protein-3, and the aminoterminal procollagen III peptide but not with changes in body composition. It is suggested that the stimulating effect of GH on EE occurs gradually during a 2-week period and is only detectable during night and morning hours, when significant levels of GH occur.

Inhibition of retrograde axoplasmic transport in rat optic nerve by increased IOP in vitro.

Horseradish peroxidase (HRP) injected into one lateral geniculate nucleus of hooded rats, is taken up by terminals of the optic nerve and transported retrogradely towards the opposite retina. Four hours after injection, a small portion of HRP has reached the retina. After excision of the bulb and optic nerve and another 4 hours of in vitro transport during which different levels of intraocular pressure (IOP) were set, more HRP accumulated in the retina. The amounts entering in vitro at IOPs of 35 and 50 mmHg were 29% and 76% less, respectively, than at 20 mmHg. The lamina cribrosa of the rat strain used was studied by scanning electron microscopy. It consisted of only one complete laminar sheet, a fact that minimizes optic nerve fiber strangulation by laminar shearing in raised IOP. Thus, moderately increased IOP can inhibit fast retrograde transport of HRP in the optic nerve of the rat by direct mechanical pressure, and does not involve either the blood circulation or a multilayered structure of the lamina cribrosa.

Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults.

The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.

Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats.

UNLABELLED: Rats were trained in a T-shaped maze to discriminate the effects produced by i.p. injections of tetrahydrocannabinol (THC) and the no-drug state (state-dependency, StD). Several doses of both Delta8-THC (range: 0.75-5.0 mg/kg) and Delta9-THC (range: 0.75-40.0 mg/kg) were used in order to compare the number of sessions required by the animals until reaching criterion performance. An additional group of rats had to discriminate pentobarbital sodium (20.0 mg/kg) from the no-drug state. RESULTS: THC discrimination was proportional to dose i.e., animals that had to differentiate high doses of THC from no drug acquired the T-maze task faster than animals trained with the lower doses of THC. Acquisition data further suggest that Delta8-THC is somewhat less potent than the Delta9-isomer. Delta9-THC (10.0 mg/kg) produces strong StD, as defined by Overton (1971), since both this group and the barbiturate group reached the criterion within the first 10 training sessions. Time and dose testings suggest that stimulus properties of drugs vary in a quantitative way and that the calculated ED50 values are mainly determined by the training dose used. It was found that the higher the training dose used the higher was the corresponding ED50 value. Hashish smoke can maintain drug responding among THC-trained rats. A lowered content of brain catecholamines and/or serotonin, induced by AMPT (150 mg/kg) and PCPA (310-350 mg/kg), did not lessen Delta9-THC (2.5 mg/kg) discrimination.

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults: I. Effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis.

Recombinant human growth hormone (GH) is routinely administered as daily subcutaneous injections to patients with GH deficiency (GHD). However, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on longitudinal bone growth, serum insulin-like growth factor-I (IGF-I) concentrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well-documented GH-dependent factors. Recombinant human GH (0.25 U/kg/wk) was administered to nine men with GHD for 14 days in two different ways, ie, as a daily subcutaneous injection at 8 PM and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. An oral glucose tolerance test (OGTT) was performed on day 0 and day 14. Daily injections and continuous infusion of GH exerted similar effects in terms of body weight and body composition. The two modes of administration resulted in similar daily urinary GH excretion and similar serum GH concentrations in the morning. GH binding protein (GHBP) concentrations did not change significantly during the various treatment periods. Serum IGF-I and IGF-I binding protein (IGFBP)-3 concentrations increased to a greater degree during continuous infusion of GH versus daily injections. Serum IGFBP-I concentrations decreased to a similar degree during the two modes of administration. Serum concentrations of free triiodothyronine and total triiodothyronine (T3) increased and free thyroxine (T4) decreased to a similar degree, independent of the mode of administration. However, total T4 concentrations were unchanged during both modes of treatment. Serum thyrotropin (TSH) concentrations decreased during continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels increased during treatment with only daily injection of GH, but there was no significant effect from continuous infusion. Results of measurements of fasting concentrations of blood glucose and oral glucose tolerance (OGT) indicated a more impaired glucose tolerance after daily injections of GH versus continuous infusion. In conclusion, continuous infusion and daily injections of GH have similar effects on the variables described, but the magnitude of the effects differs.

Growth hormone-deficient adults are insulin-resistant.

Patients with growth hormone deficiency (GHD) have traditionally been described as having increased insulin sensitivity with a tendency toward fasting hypoglycemia, at least in children. In other studies, impaired glucose tolerance has been found. To evaluate basal insulin sensitivity, a hyperinsulinemic, normoglycemic clamp was performed with an insulin rate of 40 mU/m2/min after an overnight fast. Fifteen patients (four women and 11 men aged 20 to 62 years) with GHD for at least 1 year were compared with 15 healthy controls matched for sex, age, and body mass index (BMI). Thirteen patients had complete pituitary deficiency and were being treated with conventional hormone replacement therapy. Two men had isolated GHD since childhood. Four men were being treated with bromocriptin. There were no significant differences between fasting blood glucose (4.4 +/- 0.1 v 4.7 +/- 0.2 [mean +/- SEM] mmol/L) or fasting plasma insulin (9.5 +/- 1.4 v 8.8 +/- 1.1 mU/L) in patients and controls, respectively. Fasting free fatty acid (FFA) levels were lower in patients (444 +/- 35 v 796 +/- 94 mumol/L, P < .01). Blood glucose levels during the clamp were similar (4.6 +/- 0.1 v 4.9 +/- 0.1 mmol/L), as were insulin levels (81 +/- 4 v 93 +/- 4 mU/L). A decrease in glucose infusion rate (GIR) was seen during the clamp in GHD subjects (3.9 +/- 0.5 v 9.9 +/- 0.7 mg/kg body weight/min) as compared with controls (P = .001). Even if corrections were made for body fat, there was a significant difference (GIR corrected per lean body mass, 5.8 +/- 0.8 v 13.9 +/- 0.9 mg/kg lean body mass/min, P < .001). The results suggest that adults with GHD are insulin-resistant. Despite this finding, normal fasting plasma insulin levels were seen.

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. II. Effects on serum lipoproteins and lipoprotein and hepatic lipase activity.

Recombinant human growth hormone (GH) administered as daily subcutaneous (SC) injections has been shown to affect serum lipoproteins in GH-deficient subjects. However, the effects of continuous infusion of GH on serum lipoproteins have not been investigated in GH-deficient adults. The aim of the present study was to compare effects of daily injections and continuous infusion of GH on lipoprotein metabolism. Recombinant human GH (0.25 U/kg/wk) was administered to nine GH-deficient adult men during a period of 14 days in two different ways, ie, as a daily SC injection at 8:00 PM and as a continuous SC infusion, with 1 month of washout between the treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. Abdominal SC adipose tissue lipoprotein lipase (LPL), postheparin plasma LPL, and hepatic lipase (HL) activity were measured 120 minutes after the intake of 100 g glucose. Adipose tissue LPL activity decreased and postheparin plasma HL activity increased after 14 days of GH treatment irrespective of the mode of GH administration, whereas GH treatment had no effect on postheparin plasma LPL activity. Serum triglyceride and very-low-density lipoprotein (VLDL) triglyceride concentrations increased during GH treatment. However, VLDL triglyceride concentrations increased to a greater degree during treatment with daily GH injections than during continuous infusion of GH. Serum apolipoprotein (apo) B and low-density lipoprotein (LDL) cholesterol concentrations decreased during treatment with daily GH injections, but were not significantly affected by continuous GH infusion. Thus, apo B and LDL cholesterol concentrations were lower after daily GH injections versus continuous GH infusion. Serum lipoprotein(a) [Lp(a)] and apo E concentrations increased during both modes of GH treatment. However, continuous infusion of GH resulted in a more marked increase in Lp(a) and apo E concentrations than daily GH injections. Minor effects were observed on serum apo A-I concentrations but high-density lipoprotein (HDL) cholesterol concentrations were not affected. In conclusion, GH treatment of GH-deficient men influenced adipose tissue LPL and postheparin plasma HL activity, as well as serum lipoprotein concentrations. Moreover, continuous GH infusion and daily GH injections differed with respect to the magnitude of effects on several lipoprotein fractions including VLDL triglycerides, LDL cholesterol, apo B, apo E, and Lp(a) concentrations.

Modulation of NK cell activity by moderate intensity endurance training and chronic ethanol consumption.

Chronic ethanol consumption can suppress natural killer (NK) cell activity. Exercise after ethanol administration may enhance blood ethanol clearance, which may benefit the immune response. This study examined the effects of moderate intensity endurance training and chronic ethanol consumption (20% wt/vol) on splenic NK cell activity. Mice were assigned to one of four groups: sedentary, water drinking (SED-H2O); sedentary, ethanol consuming (SED-EtOH); trained, water drinking (TR-H2O), and trained, ethanol consuming (TR-EtOH). TR groups ran 60 min/day, 5 days/wk, at 12 m/min for 10 wk. Mice were killed 48 h after exercise. Baseline NK cell activity was suppressed 30% in TR and EtOH groups compared with SED-H2O controls. Activation with recombinant human interleukin-2 increased cytolytic activity in all groups four- to fivefold. These results indicate that training did not abrogate the effects of chronic ethanol consumption on NK cell activity. Furthermore, moderate endurance training may contribute to suppressed nylon wool-enriched NK cell activity in murine splenocytes for as long as 48 h after exercise.

Mechanistic differences in NK cell cytolytic activity in treadmill-trained and chronic ethanol-consuming mice.

The present study was undertaken to investigate mechanisms contributing to differences in natural killer (NK) cell activity in moderately endurance-trained and ethanol-consuming mice. Independent of ethanol exposure, NK cell activity in nylon wool-nonadherent (NWNA) splenocytes is lower in trained than in sedentary control mice (Blank et al. J. Appl. Physiol. 72: 8-14, 1992). Reduced activity may result from a generalized loss of cytolytically active cells, redistribution of NK cells from the spleen to other body compartments, or disruption of paracrine regulation of NK cells after removal of nylon wool-adherent cells. To examine these possibilities, NK cell cytolytic activity was determined in nonenriched splenocytes from treadmill-trained and ethanol-consuming mice. Lymphocyte subpopulations in nonenriched splenocytes and NWNA splenocytes were also compared. Peripheral blood lymphocyte subpopulations were determined to examine combined effects of training and ethanol intake on regional distribution of lymphocytes in blood and spleen. NK cell activity in nonenriched splenocytes from trained water-drinking mice was not reduced compared with that in sedentary mice; rather, cytolytic activity was moderately enhanced (17% increase in lytic units, P < 0.05). Training did not change percentages of T-cells, B-cells, and NK [NK1.1+ and large granular lymphocytes (LGL-1+)] cells or the LGL/NK ratio in the spleen and blood. NK cell cytolytic activity was significantly reduced in nonenriched splenocytes from ethanol-consuming mice, independent of training. These findings support the hypothesis that moderate-intensity endurance training influences splenic NK cell function by modulating paracrine regulation of NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Diazepam as a discriminative cue: its antagonism by bemegride.

Gerbils trained to respond differentially to the presence or absence of diazepam (8.0 mg/kg) in a T-maze showed a dose-related antagonism when challenged with bemegride (5.0-40.0 mg/kg). Gerbils trained with a mixture of diazepam (8.0 mg/kg) and bemegride (20.0 mg/kg) evidenced response control more slowly than the group trained solely with diazepam.

Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors.

Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model.

Delta 9-tetrahydrocannabinol produced discrimination in pigeons.

In an operant situation pigeons learned to peck one response key 90 min after an injection of 0.25mg/kg delta9-tetrahydrocannabinol (delta9-THC) and another key when trained nondrugged. When tested with doses of delta9-THC lwer than the training dose the birds disciminated 0.20 mg/kg of the drug from the nondrugged state but not 0.15 mg/kg or lower doses. The animals were able to discriminate the drug state from the nondrugged 180 min but not 360 min after the injection At a shorter interval (45 min) both drug and nondrug responding appeared. Cannabinol and cannabidiol (4.0 - 8.0 mg/kg) did not elicit any drug responses, nor did pentobarbital, ditran or amphetamine. Tests with LSD resulted in both drug and nondrug responding. When administering noncannabinoid drugs in combination with delta9-THC 0.15 mg/kg the birds responded at the key associated with the drug state, suggesting interactional effects.

Delta9-tetrahydrocannabinol and pentobarbital as discriminative cues in the Mongolian Gerbil (Meriones unguiculatus)

Male Mongolian gerbils were trained to escape electric shocks in a T-shaped maze contingent upon the presence or absence of certain drug effects (state-dependency; StD). The drug discriminative cues used were those of either delta9-tetrahydrocannabinol (THC) or pentobarbital (P-barb.) vis-à-vis the respective vehicles. Several doses of THC (0.5-16.0 mg/kg) were used and compared with P-barb. (20.0 mg/kg), a dose at which the most rapid drug discrimination occurs in the rat. When drug discrimination was established dose-time- and transfer characteristics for the training drugs were studied. Possible potentiation and antagonism was also examined in the pentobarbital trained gerbils. It was found that none of the THC doses were discriminated as rapidly as that of P-barb. Decreasing the amounts of training drug administered or increasing the injection-test intervals resulted in a decline of the number of drug associated choices. There was a maximum of 40% drug choices between THC and P-barb at the transfer tests. Mixtures of the two compounds increased the number of drug choices in an additive or even more than additive manner. Amphetamine (4.0 mg/kg) did not interact with the P-barb. induced choice responding. The analeptic drug, bemegride was found effective in antagonizing the P-barb. cued choice behavior.

The lamina cribrosa in the eyes of rats, hamsters, gerbils and guinea pigs.

The scleral lamina cribrosa in the eyes of adult rats, hamsters, gerbils and guinea pigs was examined by ordinary histology and by scanning electron microscopy after soft tissue digestion. The complexity of the lamina, when mounted for scanning electron microscopy, was graded on a scale of 0 to 4.5 by three independent observers under X 60 magnification in a stereo microscope. The observers were unaware of the species and were offered the 44 specimens twice in random order. The average variance attributable to an observer was 22 +/- 3% (SE) of the total variance of the gradings. The rat eyes had the least developed lamina cribrosa, with only 1-2 layers of sparse connective tissue. The mean complexity grading of 12 rat eyes was 1.6 +/- 0.15. The lamina cribrosa of the eyes of gerbils and guinea pigs was much more developed with at least 3 layers of abundant connective tissue, the mean grades of complexity being 3.4 +/- 0.09 and 3.5 +/- 0.15, respectively, in 12 eyes of each species. The lamina cribrosa in the hamster eyes was somewhat more developed than that of the rat, but much less than that of the gerbil and guinea pig. The mean grade of complexity was 2.4 +/- 0.14 in 8 eyes. In 6 pairs of rat eyes there was no correlation in grade of laminar complexity between the two eyes of the same animal. The present study makes the rat eye a candidate for experiments where a possible influence of the lamina cribrosa as such is undesired.

Retrograde axoplasmic transport in rat optic nerve in vivo. What causes blockage at increased intraocular pressure?

The effect of intraocular pressure (IOP) on retrograde axonal transport of horseradish peroxidase (HRP), from the geniculate body to the retina, was studied in the rat in vivo. In 2-hr experiments (17 eyes at 50 mmHg; 13 eyes at 15 mmHg), the pressures were set just prior to the expected HRP arrival into the eyes. In 4.5-hr experiments (24 eyes at 50 mmHg; 21 eyes at 15 mmHg), the pressures were set 2.5 hr before expected HRP arrival. HRP was measured in the retinas 5 hr after the intrageniculate injection. Transport blockage occurred at an IOP of 50 mmHg in both series of experiments. In an earlier study of axonal transport in vitro, an IOP of 50 mmHg also blocked retrograde HRP transport. In a third series of experiments, 15 eyes were set at an IOP of 180 mmHg for 10 min, 10-20 min before expected arrival of HRP into the eye, while 17 control eyes were set at 15 mmHg. After the 10 min, both groups of eyes were set at 15 mmHg for another 2 hr and the HRP content in the retinas measured, 5 hr after HRP injection. There was no significant difference between these two groups of eyes, suggesting either no rapidly occurring block or a rapid recovery of transport after the high-pressure period. It is proposed that optic nerve fibers are stretched and narrowed near or at their exit, by the high IOP, but recover their shape soon after IOP is normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition and recovery of retrograde axoplasmic transport in rat optic nerve during and after elevated IOP in vivo.

Horseradish peroxidase (HRP) injected into one lateral geniculate nucleus of male inbred PVG/Mol hooded rats is taken up by terminals of the optic nerve and transported retrogradely towards the opposite retina. One hr after injection, the eyes were cannulated and set at an intraocular pressure (IOP) of either 35 mmHg or 15 mmHg. The IOP were set for 4 hr at which time the trial was terminated and retinal HRP content measured. It was found that in eyes set at 35 mmHg (18 eyes) the axoplasmic transport was partially blocked compared with that in eyes set at 15 mmHg (10 eyes), absorbances were 0.034 +/- 0.003 (S.E.) and 0.044 +/- 0.003 (S.E.), respectively, P less than 0.05. In a third group of eyes (nine eyes) set at 50 mmHg for 2 hr (beginning 1 hr after the intrageniculate injection), succeeded by another 2 hr of 15 mmHg IOP, there was no statistically significant difference in retinal HRP content compared to that in eyes set at 15 mmHg throughout, absorbances were 0.040 +/- 0.006 and 0.044 +/- 0.003, respectively. Two hr of 50 mmHg IOP blocks the axonal transport in the rat optic nerve (Johansson, 1986a). The result shows that also moderately increased IOP blocks axonal transport in the rat optic nerve. It also shows the presence of a rapid recovery when the pressure is normalized. A direct mechanical factor underlying axonal transport blockage is proposed.

Influence of low IOP and low calcium on retrograde axoplasmic transport in rat optic nerve in vitro.

Horseradish peroxidase (HRP) injected into one lateral geniculate nucleus of male inbred PVG/Mol hooded rats is taken up by terminals of the optic nerve and transported retrogradely towards the opposite retina. Four hours after injection when a small portion of HRP had reached the retina, the eye and optic nerve were excised and incubated in vitro at 38 degrees C for another 3.5 hr during which the intraocular pressure (IOP) was set at 30 or 0 mmHg. During the in vitro period additional HRP entered the retina by axonal transport if the incubation medium contained enough Ca2+. Transport occurred at 0.45-1.1 mM Ca2+, but not at 0.30mM Ca2+. When transport occurred, no significant difference in degree of transport was found between the two pressures. The amount of HRP transported at 30 and 0 mmHg was very similar to that at 20 mmHg but significantly higher than that at 50 mmHg, (values at 20 and 50 mmHg from an earlier study). Thus, fast retrograde HRP transport was equally efficient at or near a physiological IOP as at zero pressure. Also, the degree of transport inhibition was not proportional to the height of the IOP, but started to increase above 30 mmHg. This is probably due to the presence of supporting tissue in the optic nerve head and inherent strength of the nerve fibers themselves. The lamina cribrosa in the rat eye is poorly developed and a shearing force on the nerve fibers due to laminar hole misalignment can largely be excluded. Effects on blood circulation are also excluded by the in vitro situation.