The flow rate of the elastomeric balloon infusor is influenced by the internal pressure of the infusor.

The purpose of this study was to evaluate the flow rate of elastomeric balloon infusor composed of rubber or silicone materials. Two models were studied: the Baxter Twoday Infusor and Advance Silicone Infusor. Each infusion device has a preset flow rate of 2 mL/hr. Fifteen units of each device were filled with 100 mL of normal saline. The flow rate was measured gravimetically using an electronic balance. The internal pressure of the balloon infusor was measured with a Digital pressure meter via the pressure transducer. The monitored internal pressure of the two kinds of infusor was not maintained uniformly during the entire delivery period, which was divided into 3 phases: the phase of decreasing, maintained, and increasing pressure during the delivery of drug. Both devices initially infused at a relatively high rate, followed by a somewhat steady flow rate. The flow rate distinctly increased in the small residual volume. The flow rate of the balloon infusor used in this study was not sustained uniformly during the entire delivery period and was in proportion to the internal pressure of the infusor regardless of the materials.     

Block of the N-methyl- -aspartate receptor by phenycyclidine-like drugs is influenced by alternative splicing

N-methyl- -aspartate (NMDA) receptors were expressed in Xenopus oocytes from injected mRNA. The presence of an alternatively-spliced insertion encoding 21 amino acids at the N-terminus of the NMDAR1 (NR1₁₁₁) subunit, made homomeric assemblies of the receptor more sensitive to ketamine and MK-801 than receptors assembled from NMDAR1 subunits lacking this insert (NR1₀₁₁ and NR1₀₀₁). The influence of this insert was maintained when NR1 subunits were co-expressed in heteromeric combinations with NR2B. The increased sensitivity of the receptors containing the insert (NR1₀₀₁) was accompanied by a faster on-rate for drug action than was observed for receptors lacking the insert (NR1₀₁₁ and NR1₀₀₁). Our results suggest that the action of phencyclidine-like drugs is influenced by the presence of Insertion I in the NMDA isoforms, generated by alternative splicing.     

Effects of chronically administered antidepressant drugs on animal behavior

We reviewed the literature about the effects of chronically administered antidepressant drugs on animal drive-related behaviors that are increased by platform REM Sleep Deprivation (RSD): intracranial self-stimulation, locomotion, aggression, feeding, grooming and sex. We found no previous review of behavioral effects of chronic antidepressant drugs; about 200 papers on behavioral effects of one dose of antidepressant drugs; and only 14 papers on behavioral effects of chronically administered antidepressant drugs. With one dose, antidepressant drugs usually did not increase animal behaviors. With chronic administration, antidepressant drugs increased intracranial self-stimulation, locomotion, and affective aggression. Chronic drug effects on feeding, grooming, and sex were not studied. These findings are consistent with the hypothesis that antidepressant drugs increase animal drive-related behaviors by RSD because RSD precedes tested behavior with chronic drug administration but not with one dose. The findings, plus a critical review of RSD by pendulum and by midbrain stimulation, support the hypotheses (1) that in animals all methods of RSD increase drive-related behaviors; and (2) that in humans antidepressant drugs improve depression by RSD which enhances such behaviors.     

Endurance exercise performance in acute hypoxia is influenced by expiratory flow limitation

Purpose

We sought to determine if expiratory flow limitation influences intensive aerobic exercise performance in mild hypoxia.

Methods

Fourteen trained male cyclists were separated into flow-limited (FL, n = 7) and non-FL (n = 7) groups based on the extent of expiratory flow limitation exhibited during maximal exercise in normoxia. Participants performed two self-paced 5-km cycling time trials, one in normoxic (F _IO₂ = 0.21) and one in mild hypoxic (F _IO₂ = 0.17) conditions in a randomized, balanced order with the subjects blinded to composition of the inspirate. Percent change from normoxia to hypoxia in average power output (%ΔP _TT) and time to completion (%ΔT _TT) were used to assess performance.

Results

Hypoxia resulted in a significant decline in estimated arterial O₂ saturation and decrements in performance in both groups, although FL had a significantly smaller %ΔP _TT (?4.0 ± 0.5 vs. ?9.0 ± 1.8 %) and %ΔT _TT (1.3 ± 0.3 vs. 3.7 ± 0.9 %) compared to non-FL. At the 5th km of the time trial, minute ventilation did not change from normoxia to hypoxia in FL (3.4 ± 3.1 %) or non-FL (2.3 ± 3.7 %), but only the non-FL reported a significantly increased dyspnea rating in hypoxia compared to normoxia (~9 %). Non-FL athletes did not utilize their ventilatory reserve to defend arterial oxygen saturation in hypoxia, which may have been due to an increased measure of dyspnea in the hypoxic trial.

Conclusion

FL athletes experience less hypoxia-related aerobic exercise performance impairment as compared to non-FL athletes, despite having less ventilatory reserve.

     

The effect of in situ formation of antigen-antibody complexes in the glomerulus on subsequent glomerular localization of passively administered immune complexes.

In situ formation of antigen-antibody complexes in the mouse glomerulus was found to enhance the deposition of immune complexes subsequently injected passively. Administration of a large antigen excess to mice that had been given pre-formed immune complexes following in situ complex formation resulted in an apparent mobilization of immune deposits as compared to mice given pre-formed complexes alone, where no such mobilization occurred.     

Uptake of intravenously administered soluble immune complexes by type I alveolar cells and macrophages in mice

Mice (C57BL/6, n = 5) were given a single intravenous injection of soluble bovine serum albumin (BSA)-rabbit anti-BSA immune-complexes (IC) prepared at five-fold antigen excess. The mice were sacrificed 15 and 30 min, and 1, 2, 4 and 12 h after injection. Granular immunofluorescence for BSA and rabbit IgG, in a pattern consistent with IC aggregation, was observed in the alveolar walls and in the cytoplasm of alveolar cells. Moderate immunofluorescence was observed 15 min after IC injection and maximal immunofluorescence was observed at 30-60 min which decreased rapidly 2 h after IC administration. Only a trace amount of immunofluorescence was observed at 4 h and none was seen at 12 h. Light microscopic immunoperoxidase staining showed localization of IC in the interstitium of the alveolar septa and in type I alveolar cells and alveolar macrophages. By immunoelectronmicroscopy, the uptake of IC in the cytoplasm of type I alveolar cells and alveolar macrophages was confirmed.     

Dynamic exercise in man as influenced by experimental restriction of blood flow in the working muscles

The effects of reduced muscle perfusion pressure on dynamic exercise performance and cardiovascular and respiratory functions were investigated. Eight subjects were studied during supine cycle ergometry at stepwise increasing workloads until exhaustion with and without the legs exposed to a supra-atmospheric pressure of 50 mmHg (Leg Positive Pressure, LPP), a novel and convenient means of reducing the perfusion pressure in the working muscles. In the LPP condition exercise performance was reduced by 40% which, judging from assessments of perceived exertion, was due to premature muscle fatigue, indicating local or overall underperfusion of the working muscles. At any given work load, the arterial pressure response was considerably stronger during LPP than in the control condition. LPP also caused greater increases in blood lactate concentration and pulmonary ventilation, the differences from control increasing with the work load. Furthermore, the ventilatory equivalent for O₂ at a given work load was markedly higher in the LPP than in the control condition, while exercise-induced decreases in end-tidal P_CO2 were considerably exaggerated by LPP. The augmented pressor response during flow-restricted exercise, together with the strong ventilatory response which was out of proportion to overall O₂ uptake, suggests increased activation of muscle chemoreflexes by accumulation of metabolic end products, the increased pressor response tending to reduce the local flow error in the working muscles.     

Levamisole augments the cytotoxic T-cell response depending on the dose of drugs and antigen administered.

The effects of levamisole on the immune of cytotoxic thymus-derived lymphocytes were studied. An optimum relative dose of antigen and and lavamisole appears to be crucial for levamisole to augment development of cytotoxic cells.     

Stability and inactivation of mutagenic drugs and their metabolites in the urine of patients administered antineoplastic therapy

Urine samples from patients administered mutagenic antineoplastic drugs are mutagenic in the Ames assay, and hence may pose a genotoxic hazard to hospital personnel or family members caring for the patient. The urine samples in the present study were tested for mutagenicity in several strains of Salmonella typhimurium that were uvr negative (TA98, TA100) or positive (TA102, UTH8413, UTH8414), and were analyzed for the presence of drugs and their metabolites using high-pressure liquid chromatography (HPLC). Urine samples from cancer patients were kept at room temperature and their mutagenicity as well as the chemical stability of the drugs was tested for a period of 14 days. It was observed that, in general, the urine remained mutagenic for the 14-day period while the parent compound degraded within the first seven days. An exception was cisplatin, which was chemically stable as platinum, but the urine decreased in mutagenicity with time. This decrease was probably the result of ligand exchange with the platinum. Inactivation methods were developed to reduce the genotoxic hazard posed by the mutagenic compounds in the urine. Cisplatin was inactivated by complexing with sodium diethyldithiocarbamate (DDTC). Oxidation of urine containing mitomycin C and doxorubicin (sodium thiosulfate must be added to urine containing doxorubicin) with 5.25% sodium hypochlorite solution (bleach) results in mutagenic inactivation. Urine containing cyclophosphamide and its metabolites was oxidized with alkaline potassium permaganate and the active degradation products trapped with sodium thiosulfate. Both chemical and mutagenic assays are necessary to determine the reduction of risk. Methods of inactivation of mutagenic urine developed in this study are both effective and practical for the reduction of exposure to genotoxic hazards.     

The perceived duration of emotional face is influenced by the gaze direction

The present research investigates the effects of gaze direction on the perceived duration of the presentation of angry and happy expressions. When the facial expression was angry, a straight gaze elongated the perceived duration of the expression compared with an averted gaze. However, there was no effect of gaze direction when the facial expression was happy. These findings indicate that the subjective estimation of time is elongated when the observer encounters a socially important survival signal, considering that an angry face with a straight gaze may be perceived as a threat requiring a fight-or-flight response.     

Effect of some intracerebrally administered drugs on a conditioned reflex in the cat.

Injection of carbachol into the anterior hypothalamus or thalamus (intralaminar nuclei) in freely-moving cats caused a dose related inhibition of alimentary conditioned reflex performance (CRP). The inhibition directly correlated with the intensity of the emotional (rage) reaction also elicitable by carbachol from these parts of the brain. The inhibition of CRP after intrahypothalamic or intrathalamic carbachol application seemed to be a secondary effect due exclusively to the altered emotional state of the animal. Injection of carbachol into the dorsal or ventral hippocampus as well as the basal or central part of the amygdala also inhibited CRP. This inhibitory effect could only be observed when the EEG pattern of the animals showed local or propagated seizure discharges. Thus the inhibition of CRP after intralimbic carbachol application seemed to be a secondary effect due to pathologic alterations in the electrical activity of the brain. All the above effects of carbachol were easily counteracted by topical pretreatment with a few μg of atropine. Nicotine and noradrenaline were ineffective in all regions investigated.