Micropuncture measurements of interstitial fluid pressure in normal and inflamed gingiva in rats. Interstitial fluid pressure (IFP) in normal and inflamed gingiva of rats was measured by sharpened glass capillaries (diameter 2-4 microns) connected to a servocontrolled counterpressure system ad modum Wiederhielm. Gingival inflammation was induced by a steel ligature placed unilaterally around the first maxillary molar. After 8 weeks, the ligature was removed and measurements of IFP in normal and experimentally inflamed gingiva were made by puncture through the intact oral epithelium. Average IFP on the control side was 3.5 mm Hg in free, and 7.4 mm Hg in attached gingiva. Compared to the control side, IFP on the experimental inflamed side was elevated significantly (p less than 0.05) both in free and attached gingiva. In the ligated inflamed side IFP in free gingiva averaged 6.7 mm Hg, whereas in attached gingiva it showed a mean value of 10.4 mm Hg. Histological examinations showed a dense infiltrate of inflammatory cells in the connective tissue, while the contralateral control side showed normal features of epithelial and connective tissue. The present finding of increased IFP in the inflamed gingiva may in theory contribute to augmented crevicular fluid flow during inflammation.


Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. Collagenolytic enzymes released by neutrophils are associated with the destruction of periodontium in periodontal diseases. Measurement of these enzymes in gingival crevicular fluid (GCF) could be used to test for periodontal diseases and thereby simplify diagnosis. To test this hypothesis, gelatinase (MMP-9) was analyzed in GCF samples with a simple assay system. GCF was collected by a mouthrinse method from 10 patients with gingivitis (G); 10 well-treated and maintained periodontitis patients (TP) without detectable loss of attachment; and 9 patients with recurrent loss of periodontal attachment (greater than 2 mm) and/or abscess formation (RP). Clinical measurements including tooth mobility (MOB) and gingival attachment level (GAL) were made monthly for a maximum of 10 months. Active and latent forms of gelatinase were measured by a functional assay using gelatin substrate-gel enzymography and the activities were quantified by laser densitometry. Reproducibility analysis demonstrated that the assay (inter-gel, inter-assay, inter-scan) and diurnal variations were small compared to biological variation. The presence of active gelatinase was detected in 97.8% of TP samples, 86.4% of RP samples, but in only 11.4% of G samples. In addition, the mean active gelatinase activity was found to be significantly higher (p less than 0.001) in the RP (71,006 U) than the TP (43,814 U) groups, both of which were higher (p less than 0.001) than the G group (2824 U). During periods of attachment loss, samples from the RP group exhibited a 2-fold increase of mean active gelatinase activity (129,414 U).(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of titanium implant abutment surface irregularities on plaque accumulation in vivo. The purpose of this study was 2-fold to: 1) evaluate in vitro the surface texture of titanium implant abutments after exposure to plastic scalers, an air-powder abrasive system, rubber cup polishing with flour of pumice, and untreated control abutments; and 2) compare plaque accumulation in humans on abutments treated with the above methods. In part I, 5.5 mm abutments were instrumented for 30 seconds per 90 degrees segment with the respective methods. The surface character was compared to untreated controls using SEM at 260X magnification. The control abutments revealed prominent milling marks and small pits; plastic scalers slightly smoothed the milling marks and created microscratches; the air-powder abrasive largely obliterated the milling marks and caused some surface pitting; the rubber cup with flour of pumice removed the milling marks and created a smooth swirl pattern. None of the instrumentation appeared to roughen the surface. In the clinical experiment (part II), four abutments, one of each type, were placed in 12 patients for a period of 7 days, during which the patients performed no oral hygiene. At the end of 7 days, the abutments were retrieved and processed for SEM. A digitizer and software program were used to determine the percent of total abutment surface area covered by plaque. The demarcation of supragingival and subgingival plaque was well delineated. The total mean percent surface area of plaque ranged from 52.06% for the air-powder abrasive to 55.29% for the plastic scalers.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of subgingival irrigation with chlorhexidine during ultrasonic scaling. This study examines the effect of a chlorhexidine irrigant during ultrasonic scaling and root planning and compares clinical results with those obtained using a water irrigant. The irrigant was delivered either through a conventional or a recently-introduced ultrasonic scaler, which allows the irrigant solution to be passed through the inside of the scaler tip. The study utilizes a split-mouth design and contrasts the effectiveness of both instruments in improving periodontal health, as measured by standard clinical indices. A preliminary investigation of patient tolerance to treatment performed throughout the clinical trial was also undertaken. Statistical analysis at the 3 and 6 month post-treatment stage revealed no significant differences between the 4 experimental groups in respect of probing attachment levels (P > 0.5), bleeding index (P > 0.1), or plaque index (P > 0.05). Clinical attachment gain assessed by probing ranged from 0.6 to 0.9 mm. Chlorhexidine increased patient tolerance in 77% of cases and the new model ultrasonic scaler was favored over the traditional model in 70% of cases. The magnitude of the tolerance differences was however not statistically significant. The possible potential of the new scaler and of chlorhexidine as an irrigant to reduce patient discomfort is worthy of further investigation than was possible in this study.


Serum levels of tetracycline during treatment with tetracycline-containing fibers. Four adult patients with at least 8 teeth that had attachment loss of 5 to 10 mm which bled on probing were included in this study. Polymeric tetracycline (TCN) containing fibers were placed and left in the pockets for a period of 10 days. Plasma samples were collected at baseline, 1 hour, 3 hours, 3 days, and 10 days after fiber placement. The mean length of fiber used averaged 187 cm with a range of 160 to 222 cm. The maximum TCN dose per patient averaged 105 mg with a range of 91 to 126 mg producing no detectable serum level greater than 0.1 micrograms/ml. This level was found in 3 of the 4 subjects at 3 hours after fiber placement and in 1 subject at 3 days after fiber placement. Transient and insignificant levels of TCN became available systemically shortly after the placement of multiple fibers. The dose of TCN in each patient was well tolerated and was not associated with any serious adverse effects.


Efficacy of preprocedural rinsing with an antiseptic in reducing viable bacteria in dental aerosols. This double-blind, controlled, cross-over, clinical study evaluated the effect of preprocedural rinsing with an antiseptic mouthrinse on the level of recoverable viable bacteria in an aerosol generated during a typical dental procedure. Eighteen subjects participated. Following 24 hours of abstention from all oral hygiene procedures, subjects received a 10-minute ultrasonic scaling of a randomly selected one-half of their mouth which served as the unrinsed control. They were then randomly assigned either antiseptic mouthwash or a control rinse and rinsed with 20 ml for 30 seconds, after which the remaining half mouth (experimental side) was scaled ultrasonically for 10 minutes. During each 10-minute scaling period aerosolized bacteria were collected on a sterile filter using a modified vacuum air-sampling device. Microbes captured on the sterile filter were quantitated by overlaying the filters onto trypticase soy agar, incubating the filters aerobically at 37 degrees C for 24 to 72 hours, and counting the resulting colony forming units (CFU). Preliminary experiments had confirmed that neither the collection method nor residual antiseptic mouthwash in the aerosol adversely affected the number of viable bacteria recovered from the filter. Rinsing with the antiseptic mouthwash produced a 94.1% reduction in recoverable CFUs compared to the non-rinsed control, while the control rinse produced a 33.9% reduction. The difference between the mouthwash and control was statistically significant (P < .001). This study indicates that preprocedural rinsing with an antiseptic mouthwash can significantly reduce the microbial content of aerosols generated during ultrasonic scaling and may have potential in-office use as part of an infection control regimen.


Measuring clinical attachment: reproducibility of relative measurements with an electronic probe. During the past few years, improvements in detecting longitudinal changes in clinical attachment or alveolar bone density have been introduced. For example, constant-force electronic probes and computer-assisted subtraction analysis of longitudinal radiographs have been reported to be more sensitive and reproducible in detecting changes in clinical attachment or alveolar bone density, respectively. Use of these new technologies requires that sources of measurement error be identified and their contribution quantified. This study investigated the reproducibility of a constant-force electronic probe in a careful clinical setting. Measurements were performed from individually fabricated acrylic stents. Three groups of subjects were selected for the study: 10 adults without oral disease, 10 adults with gingivitis, and 10 adults with moderate periodontitis. Four probing designs were employed to investigate the reproducibility of the probe. In design A, the probe tip was left in the sulcus between successive probings. In design B, the probe tip was removed from the gingival margin between probings but the next probing followed immediately. In design C, successive whole-mouth probings were interrupted by a 5-minute interval and a mouth rinse. In design D there was a 4-week interval between each successive probing. Three measurements were taken at each site for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation ranged from 0.2 to 0.3 mm depending on the periodontal health of the subject. This level of variation is considerably smaller than that found in most previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of a number of commercial mouthrinses compared with toothpaste on plaque regrowth. Mouthwashes are frequently used as adjuncts to oral hygiene. However, for some products there is little supportive evidence that rinses provide greater benefits than plain water or additional benefits to the plaque inhibitory action provided by toothpaste. This study was a single blind, randomized, cross-over design in which 6 rinses were compared for inhibitory action against plaque regrowth. The formulations were a cetylpyridinium chloride rinse, a prebrushing detergent rinse, a peroxyborate rinse a toothpaste slurry rinse, a chlorhexidine rinse, and a saline rinse. From a zero baseline, plaque regrowth at day 5 was significantly reduced by chlorhexidine compared to peroxyborate; and, in turn, significantly reduced by peroxyborate compared to the other rinses. There were no significant differences between saline or a toothpaste slurry and the cetylpyridinium chloride or prebrushing rinse products. The findings would appear pertinent to the value of the respective rinses as adjuncts to oral hygiene.


The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. The established correlation between diabetes and periodontal diseases and the increasing prevalence of Type II diabetes in the general population indicate that dental practitioners will probably treat an increasing number of diabetic patients. Despite the fact that there is little scientific evidence to support the concept, it has been generally accepted that treatment for periodontal disease in diabetic patients may reduce insulin requirements and improve metabolic balance. However, to date no one has evaluated the effects of periodontal therapy on the metabolic state of the poorly-controlled diabetic patient. The purpose of this pilot study was to evaluate the effect of controlling gingival inflammation on blood glucose levels as determined by glycosylation of hemoglobin and albumin.


Tissue concentration and localization of tetracycline following site-specific tetracycline fiber therapy. The primary objective of this study was to evaluate the concentration and location of tetracycline hydrochloride in tissue adjacent to periodontal pockets treated with a tetracycline impregnated fiber. A secondary objective was to determine if the presurgical placement of fibers had any adverse effects on healing following periodontal surgery. The study population consisted of 10 patients with at least 2 pockets in both maxillary quadrants of > or = 5 mm in depth and exhibiting bleeding on probing. After an initial scaling and root planing, placebo or tetracycline fibers were randomly assigned by quadrant to 2 non-adjacent pockets. Fibers were removed at the time of surgery; i.e., day 8, and periodontal surgery was performed utilizing a flap incision that allowed biopsy of 1 interdental papilla from each of the 2 test sites in each quadrant. One biopsy was analyzed for tetracycline concentrations by high performance liquid chromatography (HPLC). The second biopsy was examined by both light and ultraviolet fluorescence microscopy to determine the location of residual tetracycline and the intensity of inflammatory cell infiltrates. Results showed that the tissue concentration of the antibiotic in tetracycline treated sites was 64.4 +/- 7.01 ng/mg (ng of tetracycline/mg tissue weight) which corresponds to 43 micrograms of tetracycline and was below levels of accurate measurement in placebo treated sites. Tetracycline tissue concentrations corresponded to the ultraviolet fluorescence microscopy with a Pearson correlation coefficient of r = 0.92. Tetracycline fluorescence was noted in the soft tissue wall ranging from 1 to 20 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


Psoriasis-associated periodontitis: a case report. Psoriasis with oral manifestations is rarely seen. It has been reported in the past either as an oral manifestation of this skin disease or lichen planus accompanying psoriasis. Very few periodontal lesions associated with dermatologic psoriasis have been reported in the literature. This report describes a case of psoriasis in which exacerbation of the cutaneous disease was accompanied by gingival epithelial changes and periodontal bursts, together with a report on the light microscopy of biopsies from periodontal lesions.


The dimensionality of Type A behavior within a stressful work simulation. The present study was conducted to examine the dimensionality of overt Type A behaviors elicited in a simulated stressful work environment. University students played a managerial role while being subjected to time and work-load pressures, and completed the Survey of Work Styles (SWS; Jackson & Gray, 1989). Eighteen behaviors, coded by two raters based on audiovisual recordings, yielded relatively high interrater reliabilities. Principal components analysis revealed four primary factors: Hurriedness, Irritability, Tension of the Lower Extremities, and Restlessness. These factors contribute to an understanding of Type A behavior in that they are the first to be derived from a purely observational approach rather than a combination of observational and self-report methods. Consistent with previous research, differential correlations between the factors and the SWS subscales supported a multi-dimensional interpretation of the Type A behavior pattern. Present findings are compared to those of previous studies of Type A dimensionality.


The personality of young adult couples and wives' work patterns. The influence of personality in 63 couples at the time of family formation on wives' work patterns 15 years later was examined in variable-centered and person/couple-centered ways. Four factor dimensions on the Adjective Check List assessed personality. Work patterns were assessed with measures of type, amount, and status of work and with schematic work narratives describing characters and plots abstracted from wives' mid-life data. Hierarchical regression analyses showed individuality of husbands to affect work outcomes after wives' college-age goals, their young adult personality, and the duration of marriages were taken into account. Conjoint high-low patterns of individuality in 34 couples were associated with different schematic work stories. These stories show distinctive personality and relational correlates at age 27. They flesh out and qualify hypotheses that individualistic partners would be open to women's careers and would show revealing strategies of combining self- and other interests in the transition to parenthood.


Stability of self-esteem: assessment, correlates, and excuse making. We examined stability and level of self-esteem as predictors of excuse making; the extent to which self-ratings of stability are related to a statistical index of self-esteem stability; and the relations between stability and certainty of self-esteem and a variety of other psychological constructs. Regarding excuse making, our findings indicated that for high self-esteem individuals, instability was related to greater excuse making following success, but not following failure. However, for low self-esteem individuals, instability was related to greater excuse making following failure, but not following success. Other findings indicated that self-ratings of stability were only minimally related to a statistical measure of stability based on repeated assessments of self-esteem obtained in naturalistic contexts. Finally, stability of self-esteem was not significantly correlated with certainty of self-esteem. In addition, the pattern of correlations that emerged between certainty and other constructs suggested that uncertainty reflects the phenomenal experience of a tenuous self-view. On the other hand, stability of self-esteem appears to reflect the extent to which one's self-view is malleable, which may not be completely available to conscious awareness. Our discussion focuses on the nature of self-esteem stability and the roles of stability and level of self-esteem in reactions to evaluative events.


[Ionizing treatment of food].

[Ionizing treatment of food]. After a description of the principles of the radiation treatment of food, the main applications in food industry are listed. Then, the status on possible identification methods for irradiated foodstuffs is described, with a special view on the coordinated action of the Community Bureau of Reference (CEC).


Influence of physico-chemical parameters on the release kinetics of ketoprofen from Poly(HEMA) crosslinked microspheres. This report analyses the release of Ketoprofen from Poly(HEMA) microspheres crosslinked with EGDMA at different crosslinking ratios and loaded by soaking in saturated solutions of the drug. Release appears to be influenced by the dissolution of Ketoprofen in the hydrogel and it is strictly correlated with the diffusibility of the drug in the gelled matrix. The release rate of the drug in the hydrogel rises with the increase in the diffusional conductance and the release kinetics approaches zero order particularly at the higher values of the diffusional conductance.


Comparative effects of chloroflavone congeners as inducers of hepatic microsomal monooxygenases in rats. The inductive effects of pretreatment with 10 synthetic chloroflavone isomers and congeners (80 mg/kg/d for 3 d, i.p.) on hepatic microsomal monooxygenases were examined with male Wistar rats. All chloroflavone congeners, except 3'-chloroflavone (CF), significantly increased (1.2- to 2-fold) the content of total cytochrome P-450 (P-450s) in microsomes. The effects of these congeners were evaluated based on the activities of microsomal aminopyrine N-demethylase, aniline hydroxylase and scoparone (6,7-dimethoxycoumarin) O-demethylase, and the CO difference spectrum and sodium dodecyl sulfate-gel electrophoretogram of cytochrome P-450s. The results were compared with those of phenobarbital (PB), 3-methylcholanthrene (MC) and PB plus MC. Based mainly on effects on the CO difference spectrum and ratio of the two O-demethylase activities of scoparone, 2'-CF and 2',4'-dichloroflavone (DCF) were categorized as the PB-type, 4'-CF and 6,8-DCF as the MC-type, 3',6-DCF and 3',5',6-trichloroflavone as weak MC-type, and 6-CF and 2',6-DCF as mixed (PB plus MC)-type inducers. A comparison of chloroflavone isomers and congeners indicated that (1) the presence of the 2'-chloro substituent of the flavone system is a minimal requirement for exhibiting the PB-type effect, (2) the absence of the 2'-chloro substituent is possibly that for exhibiting the MC-type effect and (3) the induction potencies by individual chloroflavone congeners may not be related to the degrees of chlorination.


[Clinical aspects of receptors; from animal models to physiopathological concepts. Experience with fenfluramine]. The fenfluramine racemate belongs to a new therapeutic class of molecules acting on food intake, without psychostimulant or addictive potential. This molecule was extensively studied in the treatment of obesity and its action was better understood by studying the dextrogyre and levogyre enantiomers. New methods allowed to show that dexfenfluramine (the dextrogyre isomer) worked through a serotoninergic activity which was responsible for the effect on food intake and disorders of eating behavior. New pharmacological concepts have emerged by using this molecule and new animal models, nearer to human pathology, were found (stress induced eating, carbohydrate selection...). Molecular Biology and Neurosciences have already led to a better knowledge of the central mechanism of action of the molecule by describing its effect on receptors and binding sites; however a lot of other concepts remain to be discovered.


The biological fate of sodium prasterone sulfate after vaginal administration. I. Absorption and excretion in rats. The absorption and excretion of sodium prasterone sulfate (PS) (sodium dehydroepiandrosterone sulfate) were studied in rats after vaginal administration of 14C-PS. In late pregnant rats, maximum plasma level (Cmax) appeared at 2-4 h after dosing and both Cmax and the area under the plasma concentration-time curve (AUC) increased proportionally with increased dose up to 4.0 mg/kg. The radioactivity administered was almost completely recovered from urine and feces during a 72 h postdosing period. The percentages of radioactivity excreted in urine and feces were 58% and 40% of the dose, respectively. The biliary excretion was 46% of the dose within 48 h and about half of the radioactive biliary excreta entered the enterohepatic circulation system. The vaginal absorption of PS was markedly affected by the estrous cycle stage and the progress of pregnancy. The vaginal absorption of PS was predominant at metestrus and diestrus and during late pregnancy.


[Mechanism of action of hypolipemic drugs]. Hypolipemic drugs decrease the plasmatic concentrations of atherogenic lipoproteins, especially LDL. Two main drug families are used: fibrates and inhibitors of HMG CoA reductase. Fibrates act essentially as an activator of lipoprotein lipase and by increasing the catabolism of triglyceride rich lipoproteins. Further, they have a slight and non specific inhibitory effect on HMG CoA reductase activity, while, the new drug family of "statines" have a high, specific inhibitory effect on this essential enzyme of the cholesterol synthesis pathway. This enzymatic inhibition decreases the cholesterol synthesis and increases the activity of the hepatic LDL receptors, which are in charge of LDL elimination from the body. Resins entrap biliary salts and increase the cholesterol loss in feces and induce an over expression of the LDL receptors of the hepatocytes. Probucol inhibits atherogenesis by decreasing both LDL and HDL cholesterol and delaying LDL oxidative processing which is now believed to be one of the major factors of atherogenicity.


YM-14673, a new thyrotropin-releasing hormone analog, augments long-term potentiation in the mossy fiber-CA3 system of guinea pig hippocampal slices. Effects of a new thyrotropin-releasing hormone (TRH) analog, N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]L-histidyl-L-prolinamide dihydrate (YM-14673), which improves experimentally induced memory dysfunction, on long-term potentiation (LTP) in the mossy fiber-CA3 system, were investigated using guinea pig hippocampal slices. At concentrations of 10(-7) M and 10(-6) M, YM-14673 significantly augmented LTP in a concentration dependent manner. The magnitude of effect of 10(-6) M YM-14673 was similar to that of 10(-6) M TRH. As LTP in the hippocampus is regarded as an elementary process of memory and learning, the augmenting effect of YM-14673 on LTP in the present study may contribute to this drug's ability to remedy memory dysfunction.


An application of microdialysis to drug tissue distribution study: in vivo evidence for free-ligand hypothesis and tissue binding of beta-lactam antibiotics in interstitial fluids. To prove the free-ligand hypothesis for extravascular equilibration and tissue binding mechanism of beta-lactam antibiotics, the microdialysis technique has been employed for the lung, the muscle and the liver in rats. Cefminox, a cephem antibiotic, and SY5555, a new penem antibiotic, were used in the present study. During the constant infusion of each antibiotic with simultaneous infusion of antipyrine, the microdialysis studies were performed and the dialysate concentrations were determined. The dialysate concentration was extrapolated to the in vivo unbound concentration in tissue interstitial fluids (Cisf,u) according to the extrapolation method which was derived from the clearance concept. This extrapolation method incorporates the effective dialysis coefficient of a reference compound, antipyrine, which is used to correct the difference between in vivo and in vitro permeabilities of microdialysis fiber. The values of Cisf,u values for cefminox and SY5555 in the lung, muscle and liver were close to the unbound concentrations in the venous plasma leaving these organs. Furthermore, good coincidences were obtained between the unbound concentrations of SY5555 in lung and muscle interstitial fluids estimated from the total concentrations in homogenized tissues and those extrapolated by the microdialysis studies. Consequently, the present microdialysis studies provided the in vivo evidence that 1) the free-ligand hypothesis for extravascular equilibration of beta-lactam antibiotics is true, and that 2) beta-lactam antibiotics are restricted in the interstitial space in a noneliminating organ and bind only with albumin existing in this space.


Coexpression of vimentin and glial fibrillary acidic protein in glial cells of the adult rat pineal gland. In the present work, coexpression of vimentin (VIM) and glial fibrillary acidic protein (GFAP) is demonstrated in the glial cells of the adult rat pineal gland. Serial consecutive Epon semithin sections (0.5 microns thick) were alternately immunostained for VIM and GFAP. GFAP positive cells and processes were found in the proximal region of the pineal gland, near the pineal stalk. Most of these cells were also immunostained for VIM in adjacent semithin sections. The significance of the coexpression VIM-GFAP and the restricted location of GFAP positive cells is discussed in relation with the maturation of pineal glial cells.


Paradoxical effects of melatonin on spontaneous neuronal activity in the striatum of sham-operated and pinealectomized rats. The acute effects of intravenous melatonin on spontaneously active striatal neurons in sham-operated and pinealectomized rats were studied. Extracellular recordings in a total of 76 neurons showed that only 19 did not modify their spontaneous activity after melatonin injection. In sham-pinealectomized rats, neural firing decreased in most cells (80% of neurons), and increased in only 5.7% of the neurons after indole administration (100 ng/kg body weight). However, in the group of rats pinealectomized 7 days earlier, the injection of melatonin (at the same dose as above) significantly increased the excitatory response (44%), while the number of cells showing inhibitory response decreased (17%). Moreover, a small percentage (4.9%) of neurons in pinealectomized rats displayed a biphasic response (initial decrease followed by an increased firing). These results demonstrate that aMT can modulate the activity of striatal neurons, and suggest that other compounds of pineal origin (e.g., vasotocin) may change effects of aMT on basal ganglia neurons.


Components of the melatonin message in the response to photoperiod of the tammar wallaby (Macropus eugenii). Female tammars experiencing long-day photoperiod (LD 15:9) are in a reproductive state termed seasonal quiescence. After a change to LD 12:12, a sequence of endocrine events, dependent on a melatonin message being interpreted during the next 3 days, leads to the disappearance of a morning pulse of prolactin on day 4, and to reactivation of the quiescent corpus luteum by day 8. Elements of the message were investigated in three experiments. In experiment 1, tammars on LD 15:9 were injected with melatonin 2.5 hr before lights out on 0-5 successive days. All those receiving four or five daily injections, and six of ten receiving two or three injections, reactivated. In experiment 2, tammars on LD 15:9 were injected with melatonin or oil on 5 consecutive days to achieve a lengthening of the period of elevated melatonin from 9.0 hr to 9.5 hr, 10 hr, 10.5 hr, and 11.5 hr respectively. One of five tammars experiencing 10 hr and seven of ten experiencing the longer periods reactivated. In experiment 3, tammars on LD18:6 received melatonin 6 hr, 6 + 3 hr or 3 hr before lights out for ten successive days. Between injections the melatonin concentrations returned to basal levels. The treatments thus provided a skeletal increase in the profile of melatonin from 6 to 9 hr or 6 to 12 hr. All those treated at 6 + 3 hr reactivated and three of five treated at 6 hr only reactivated. We conclude that the tammar stores information about the change in the maximum duration of elevated melatonin experienced each night and, after three successive periods in which the duration is greater than 10.5 hr, it reactivates. Since reactivation cannot occur until completion of the third dark phase, the processing center must be active during the fourth day, prior to the abolition of the prolactin peak.


Prolonged suppression of serum concentrations of melatonin in prepubertal heifers. Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light during the last 6 hr of their usual 12-hr nocturnal period. During this 6-hr exposure to various intensities of light, melatonin concentrations were similar to their respective daytime baseline values measured under 400 lux of light, but were 62% to 82% lower than melatonin concentrations during their nocturnal surge period. Suppression of melatonin concentrations was similar between 400 and 1,200 lux of light. In Experiment 2, heifers were exposed to LD 8:16, LD 16:8, LD 20:4, or LD 24:0 photoperiods (1,200 lux) for 4 months. Throughout treatment, concentrations and durations of the melatonin surge were suppressed in the LD 24:0 group and were greatest (during the nocturnal period) in the LD 8:16 group. Concentrations of prolactin in serum were elevated in animals under long days relative to LD 8:16 treatment and respective pretreatment periods. In conclusion, continuous light at an intensity of 1,200 lux suppressed the nocturnal surge of melatonin, but increased secretion of prolactin for at least 4 months in prepubertal heifers.


On the orienting value of attitudes: attitude accessibility as a determinant of an object's attraction of visual attention. Four experiments tested the hypothesis that objects toward which individuals hold attitudes that are highly accessible from memory (i.e., attitude-evoking objects) are more likely to attract attention when presented in a visual display than objects involving less accessible attitudes. In Experiments 1 and 2, Ss were more likely to notice and report such attitude-evoking objects. Experiment 3 yielded evidence of incidental attention; Ss noticed attitude-evoking objects even when the task made it beneficial to ignore the objects. Experiment 4 demonstrated that inclusion of attitude-evoking objects as distractor items interfered with Ss' performance of a visual search task. Apparently, attitude-evoking stimuli attract attention automatically. Thus, accessible attitudes provide the functional benefit of orienting an individual's visual attention toward objects with potential hedonic consequences.


Terror management and tolerance: does mortality salience always intensify negative reactions to others who threaten one's worldview? Terror management research has shown that reminding Ss of their mortality leads to intolerance. The present research assessed whether mortality salience would lead to increased intolerance when the value of tolerance is highly accessible. In Study 1, given that liberals value tolerance more than conservatives, it was hypothesized that with mortality salience, dislike of dissimilar others would increase among conservatives but decrease among liberals. Liberal and conservative Ss were induced to think about their own mortality or a neutral topic and then were asked to evaluate 2 target persons, 1 liberal, the other conservative. Ss' evaluations of the targets supported these hypotheses. In Study 2, the value of tolerance was primed for half the Ss and, under mortality-salient or control conditions, Ss evaluated a target person who criticized the United States. Mortality salience did not lead to negative reactions to the critic when the value of tolerance was highly accessible.


Marital processes predictive of later dissolution: behavior, physiology, and health. Seventy-three married couples were studied in 1983 and 1987. To identify marital processes associated with dissolution, a balance theory of marriage was used to generate 1 variable for dividing couples into regulated and nonregulated groups. For studying the precursors of divorce, a "cascade" model of marital dissolution, which forms a Guttman-like scale, received preliminary support. Compared with regulated couples, nonregulated couples had (a) marital problems rated as more severe (Time 1); (b) lower marital satisfaction (Time 1 and Time 2); (c) poorer health (Time 2); (d) smaller finger pulse amplitudes (wives); (e) more negative ratings for interactions; (f) more negative emotional expression; (g) less positive emotional expression; (h) more stubbornness and withdrawal from interaction; (i) greater defensiveness; and (j) greater risk for marital dissolution (lower marital satisfaction and higher incidence of consideration of dissolution and of actual separation).


Empathy: a physiological substrate.

Empathy: a physiological substrate. The relation between empathy (defined as the ability to perceive accurately how another person is feeling) and physiology was studied in 31 Ss. Ss viewed 15-min martial interactions and used a rating dial to indicate continuously how they thought a designated spouse was feeling. Rating accuracy was determined by comparing Ss' ratings with identical self-ratings obtained previously from the target spouse. Physiological linkage between S and target was determined using bivariate time-series analyses applied to 5 autonomic and somatic measures obtained from the S during the rating task and from the target spouse during the original conversation. Accuracy of rating negative emotion was greatest when S and target evidenced high levels of physiological linkage across time. Accuracy of detecting positive emotion was related to a state of low cardiovascular around in the S, but not to physiological linkage between S and target.


Accuracy in perceptions of interpersonal interactions: effects of dysphoria, friendship, and similarity. Conflicting views of depressives' interpersonal accuracy were addressed in an investigation of the accuracy of mild depressives (dysphorics) across differing social contexts. Women who were either friends or strangers and who were either similar or dissimilar in level of dysphoria conversed about 3 topics: a neutral topic, their own disclosure of a personal problem, and their partner's disclosure. Dysphorics were not more accurate in general than nondysphorics. After self-disclosure, all women more accurately detected sympathy from a similar stranger. After the partner's disclosure, women also better detected the mood of a similar partner. When interacting with nondysphoric strangers, however, dysphorics underestimated their partner's sympathy toward them. Implications for cognitive and interpersonal theories of depression and for depressives' relationships are discussed.


Psychosocial development in adulthood: a 22-year sequential study. Data supporting the notion of adult personality stability are challenged by the present findings, in which developmental change was demonstrated using the Eriksonian-stage-based Inventory of Psychosocial Development (IPD; Constantinople, 1969). A sequential design over the ages 20-42 was used on 2 cohorts of college students and alumni originally tested in 1966 and 1976-1977 (ns in 1988 = 99 and 83, respectively), and a 3rd cohort of college students in 1988-1989 (n = 292). Results of longitudinal, cross-sectional, and sequential analyses challenged ideas about personality stability, with evidence of increasingly favorable resolutions of the early Eriksonian psychosocial stages up through the oldest age studied. There was evidence of a trend over the past decade toward less favorable resolution of ego integrity versus despair. The findings were interpreted in terms of developmental change processes during the adult years interacting with culturally based environmental effects on psychosocial development.


Multiple protective and risk factors for drug use and abuse: cross-sectional and prospective findings. A conceptual elaboration was developed that incorporates many risk and protective factors, and both direct and moderating (buffering) influences on drug involvement were tested. From prospective data, 14 factors related to drug use were selected and assigned empirically to either a multiple protective index (PFI) or a risk factor index (RFI). Analyses examined the relationships of the RFI, PFI, and their interaction on measures of cigarette, alcohol, cannabis, cocaine, and hard drug use cross-sectionally in late adolescence and later in young adulthood. These same variables were used to predict alcohol, cannabis, and cocaine abuse 8 years later. Vulnerability as measured by the RFI, PFI, and their interaction was highly associated with drug use in adolescence, moderately associated with certain types of drug use in young adulthood, and strongly associated with heightened drug problems in adulthood.


General and specific support expectations and stress as predictors of perceived supportiveness: an experimental study. Fifty-four undergraduates and their mothers participated in an experiment to evaluate hypotheses derived from a theory of perceived social support (Pierce, Sarason, & Sarason, 1990). Regression analyses indicated that the variables in the model accounted for 14.83% and 40.93%, respectively, of the variance in students' perceptions of their mothers' behavior assessed during 2 standardized laboratory situations. Unique effects were found for students' expectations for support from and conflict with their mothers in both pre- and posttask situations, although the effect of conflict was contrary to prediction in the pretask situation. Stress had an impact only in the posttask situation. Students' general expectations for support had no unique impact in either situation. Implications for the role of general and specific expectations for support and conflict, and situational factors, in theories of perceived social support are discussed.


The effect of normative beliefs on anticipated emotions. In 3 experiments, Ss were asked how they would or should make hypothetical decisions and how they would react emotionally to the options or outcomes. The choices were those in which departures from proposed normative models had previously been found: omission bias, status quo bias, and the person-causation effect. These effects were found in all judgments, including judgments of anticipated emotion. Arguments against the departures affected judgments of anticipated emotion as well as decisions, even though the arguments were entirely directed at the question of what should be done. In all but one study, effects of these arguments on anticipated emotion were as strong as their effects on decisions or normative beliefs. Thus, in many situations, people think that their emotional reactions will fall into line with their normative beliefs. In other situations, some people think that their emotional reactions have a life of their own. It is suggested that both normative beliefs and anticipated emotions affect decisions.


The role of diagnosticity in stereotype formation: perceiving group means and variances. Three experiments tested the hypotheses that while forming stereotypes of social groups, people abstract the central tendency and variability of different attribute dimensions to determine which ones best differentiate the groups and that more differentiating dimensions are more likely to become stereotypical in the sense of becoming strongly associated with the groups in memory. Supporting these hypotheses. Experiment 1 found that, after viewing behaviors performed by members of 2 groups, Ss characterized the groups more in terms of attribute dimensions indicating larger differences between the central tendencies of the groups, and Experiment 2 showed that this effect did not occur when Ss formed impressions of only 1 group. Experiment 3 found that Ss also characterized groups more in terms of attribute dimensions indicating lower within-group variability.


Once a boring task always a boring task? Interest as a self-regulatory mechanism. A process was proposed through which individuals regulate their motivation to perform necessary but uninteresting activities over time. If committed to continuing, individuals may engage in interest-enhancing strategies that can change the activity into something more positive to perform. In Study 1 Ss performed novel tasks and generated strategies to make regular performance interesting. In Study 2 Ss actually used these strategies primarily in conditions indicating a self-regulatory attempt: The task was currently boring, there was a perceived reason to continue (alleged health benefit), and a relevant strategy was available. Strategy use was associated with a change in activity definition and greater likelihood of subsequently performing the activity. In Study 3 Ss beliefs about how to maintain motivation to perform more everyday activities emphasized the importance of regulating interest relative to other self-regulatory strategies.


Gender and self-esteem.

Gender and self-esteem. Where does self-esteem (SE) come from? Three experiments explored the idea that men's and women's SE arise, in part, from different sources. It was hypothesized that SE is related to successfully measuring up to culturally mandated, gender-appropriate norms--separation and independence for men and connection and interdependence for women. Results from Study 1 suggested that men's SE can be linked to a individuation process in which one's personal distinguishing achievements are emphasized. Results from Study 2 suggested that women's SE can be linked to a process in which connections and attachments to important others are emphasized. Study 3 demonstrated that failing to perform well on gender-appropriate tasks engendered a defensive, compensatory reaction, but only in subjects with high SE. These findings are discussed with regard to their implications for the structure and dynamics of the self.


Self-concept change and self-presentation: the looking glass self is also a magnifying glass. Studies 1 and 2 showed that identical behaviors had greater impact on the self-concept when performed publicly rather than privately. That is, the self-concept is more likely to change by internalizing public behavior than by internalizing behavior that is identical but lacks the interpersonal context. The self-concept change extends even to behavioral changes and occurs even when participants are unaware of being observed. In addition, those who are high in self-monitoring are more likely to internalize their behavior than those who are low in self-monitoring. Study 3 provided evidence about what components of a public situation affect the internalization of behavior. Choice about making the self-portrayal, drawing on episodes from one's own past rather than relying on a yoked script, and expecting future interaction with the audience all increased the internalization of a public behavior.


The aggression questionnaire.

The aggression questionnaire. A new questionnaire on aggression was constructed. Replicated factor analyses yielded 4 scales: Physical Aggression, Verbal Aggression, Anger, and Hostility. Correlational analysis revealed that anger is the bridge between both physical and verbal aggression and hostility. The scales showed internal consistency and stability over time. Men scored slightly higher on Verbal Aggression and Hostility and much higher on Physical Aggression. There was no sex difference for Anger. The various scales correlated differently with various personality traits. Scale scores correlated with peer nominations of the various kinds of aggression. These findings suggest the need to assess not only overall aggression but also its individual components.


Optimism, coping, psychological distress, and high-risk sexual behavior among men at risk for acquired immunodeficiency syndrome (AIDS). In a cohort of gay men responding to the threat of acquired immunodeficiency syndrome (AIDS), dispositional optimism was associated with less distress, less avoidant coping, positive attitudes as a coping strategy, and fewer AIDS-related concerns. Men who knew they were seropositive for human immunodeficiency virus (HIV) were significantly more optimistic about not developing AIDS than men who knew they were seronegative for HIV. This AIDS-specific optimism was related to higher perceived control over AIDS and to active coping among seropositive men only and to health behaviors in both serostatus groups. There was no relation of optimism to risk-related sexual behavior. It is concluded that optimism is psychologically adaptive without necessarily compromising health behavior. It is also concluded that it is useful to distinguish between event-based optimistic expectations and dispositional optimism.


The motivational and emotional consequences of considering positive or negative possibilities for an upcoming event. The hypothesis that attention to negative possibilities for an upcoming event can have advantages for performance in comparison with a more optimistic approach was examined in 2 studies. Focus of attention to positive or negative possibilities for a social interaction was manipulated for Ss previously identified as optimists or defensive pessimists in the social domain. In Study 1, negatively focused defensive pessimists performed better in their conversations than positively focused defensive pessimists on several dimensions (e.g., talk time, perceived effort, and sociability). Optimists' behavior was unaffected by the focus manipulation. However, all negatively focused Ss felt worse after their conversations than did positively focused subjects. Study 2 examined the cognitive process by which a negative focus may lead to positive behaviors. Some pessimists may benefit from an initial negative focus that is not accompanied by lowered expectations and that actually facilitates positive thoughts about the self.


Gender characteristics and adjustment: a longitudinal study. The present study used a prospective longitudinal design to investigate the long-term developmental implications of gender-related interests and traits. Archival data were available for Ss in the R. R. Sears, Maccoby, and Levin (1957) study. Men, who at age 12 endorsed interests and undesirable traits more typically associated with women, had poorer social-personal adjustment at ages 31 and 41. No effects were found for women. Feminine expressive traits at age 31 did not impact on 41-year-old adjustment for either men or women, whereas masculine instrumental traits were positively related for both. These findings support a multidimensional view of gender and indicate that harsher consequences follow when adolescent boys endorse nontraditional gender-related interests and undesirable traits than when girls do so.


The four faces of eve: a typological analysis of women's personality at midlife. In an analysis of adult personality structure, types are defined as prototypes rather than as discrete categories. Using inverse factor analyses of archival Q-sort descriptions, 4 type factors were replicated in a cross-validation design. These prototypes are interpreted as Individuated, Traditional, Conflicted, and Assured and are related to Rank's (1945) theoretical analysis of different modes of adjustment. These prototypes capture particular combinations of personality dimensions, such as Ego Resiliency, Ego Control, and the Big Five, and converge with the types identified by Block (1971). Further analyses using 13 clusters of scales from 3 broad-band self-report inventories validated the Q-sort-based interpretations and showed a distinct and theoretically consistent patterning for each of the types.


Faith in recovery. Spiritual support after an acute MI. Data from a sample of ninety AMI patients indicate that the majority of these patients find that their spiritual views are a source of help, both at hospital discharge and during early recovery at home. Conversely, a small group of these patients said they did not receive help. Since the remainder of the patients were unsure if they received help from their religious or life views, I believe that all AMI patients could benefit from spiritual care provided by Christian nurses. Findings also indicate that subjects who experienced spiritual support at home also experienced decreased stress.


Detection of incident HIV infection by PCR compared to serology. In order to determine the most sensitive method for the early detection of HIV infection, polymerase chain reaction (PCR) and serology were compared using matched peripheral blood mononuclear cells (PBMC) and serum samples taken sequentially at 3-month intervals on 17 HIV seroconverters. All samples from the time of enrollment in the study to the time of seroconversion were studied. [There were only two of the 17 cases where PCR and antigen positivity preceded EIA detectable seroconversion.] Initially, one of these cases was found to be PCR positive 11 months prior to seroconversion, however DNA fingerprinting techniques indicated that the early positive specimen did not belong to the subject in question. In a single subject, PCR was negative at the time of serologic evidence of infection but was positive at the next sampling 3 months later. In the remaining 14 cases, PCR was positive at the same sample time as full or partial seroconversion as determined by three EIA screening tests and Western blot. EIA antibody screen tests showed variability in detection of early HIV antibodies. We found no evidence for prolonged HIV infection prior to seroconversion. PCR offers little if any advantage over serology in the early detection of HIV infection in adults.


Acidification modified p24 antigen capture assay in HIV seropositives. The p24 antigen is only detectable in a minority of asymptomatic HIV infected individuals, which is in part felt to be secondary to immune complex formation with p24 antibody. We sought to determine if the recovery of p24 antigen could be enhanced by an acidification procedure in an attempt to dissociate p24 antibody-antigen complexes. We tested 291 HIV antibody positive serum samples in duplicate, comparing the standard Coulter p24 Antigen Assay with the same assay which was modified by pretreating samples for 60 min with 1.5 M glycine (pH 1.85) and then neutralizing the sample with 1.5 M Tris (pH 9.0). Using the assay cutoff (approximately 7.8 pg/ml), the standard assayed sera and the acid pretreated sera were positive in 65/291 (22.3%) and 167/291 (57.4%) of the samples, respectively. This difference between procedures was statistically significant (p < 0.0001) by McNemar chi 2. There was also a statistically significant difference between Walter Reed stages for p24 antigen quantification by ANOVA (p < 0.0001). We have demonstrated that the detection of p24 antigen may be significantly enhanced by acid pretreatment of sera which dissociates immune complexed antigen. We have also shown significant differences exist between Walter Reed stages for quantitative p24 antigen levels. Enhanced detection of p24 antigen may be important prognostically and may allow for the monitoring of antiretroviral therapy.


Cytokine dysregulation in AIDS: in vivo overexpression of mRNA of tumor necrosis factor-alpha and its correlation with that of the inflammatory cytokine GRO. The human immunodeficiency virus establishes an intimate interaction with the immune system. The virus can use cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (Il-1), to regulate its own expression by modifying the normal immunoregulatory network. We demonstrate that mRNA of the cytokine TNF-alpha from peripheral blood mononuclear cells is overexpressed in virtually all patients with AIDS who do not have active opportunistic infections compared with uninfected volunteers (p < 0.0001). This overexpression correlates with elevated mRNA levels of the recently discovered GRO (p < 0.05), a cytokine involved in the inflammatory response.


AIDS incidence and income.

AIDS incidence and income. Since 1987, the annual increases of AIDS incidence among homosexual and bisexual men have slowed but the increases among other risk groups have continued unabated. Although indirect evidence suggests the incidence change is related to medical care for HIV disease delaying the onset of AIDS, other explanations are also possible. To examine the incidence change from a different perspective, we classified the residents of Philadelphia (PA, U.S.A.) with AIDS by the per capita income of their census tracts of residence. AIDS incidence increased steadily in the lowest income tercile, showed continuing but smaller increases after 1987 in the middle tercile, and was level after 1987 in the highest income tercile. The relationship between income and changes of incidence persisted after stratification on race or mode of infection with HIV. Income was associated with private medical insurance at the time of diagnosis of AIDS (59% privately insured in the highest income tercile, 24% in the lowest) and with median survival after a diagnosis of AIDS (467 days in the highest tercile of income, 359 days in the lowest). These observations are consistent with a medical treatment benefit that reaches the highest tercile of income and does not reach the lowest one.


AIDS prevalence by income group in Philadelphia. We sought to track recent changes in AIDS incidence and prevalence in the city of Philadelphia (PA, U.S.A.) using morbidity and mortality data reported to the health department. We stratified the data by the mean per capita income in census tracts where people with AIDS resided. Estimates made without adjustment for the time lag between events and their entry into the database undercount both recent AIDS diagnoses and recent AIDS deaths. Therefore, we used a previously published method to adjust for the lag in reporting diagnoses and developed a method to adjust for the lag in reporting deaths. We calculated prevalent cases as the difference between cumulative cases and cumulative deaths. Between 1988 and 1990, annual AIDS incidence per 100,000 Philadelphia residents increased by 21% (from 25.9 to 31.4) and AIDS prevalence per 100,000 population increased by 62% (from 30.2 to 48.8). AIDS prevalence increased 113% (from 29.8 to 63.6) in low-income tracts, 88% (from 27.8 to 52.3) in middle-income tracts, and 14% (from 32.5 to 37.2) in high-income tracts. The 62% increase in AIDS prevalence and the shift toward people in poorer neighborhoods imply a need for public funding for AIDS care that is far larger than would be suggested by the general 21% increase in AIDS incidence over the same period.


A model-based estimate of HIV infectivity via needle sharing. Critical to understanding the spread of the human immunodeficiency virus via needle sharing among drug users is the infectivity, i.e., the conditional probability of infection given injection with a shared, contaminated syringe. A simple mathematical model was constructed that relates infectivity to the prevalence of infection in needles used by drug users, the mean shared injection frequency among drug users, the probability that a needle is disinfected prior to use, and the mean AIDS incubation time. Three of these parameters have been estimated using data from the New Haven, Connecticut legal needle exchange program. Using the polymerase chain reaction to test for the presence of HIV proviral DNA in a sample of returned needles, we determined that 67.5% were HIV positive. We were able to estimate shared injection rates and disinfection rates from surveys of drug users enrolled in the needle exchange and our syringe tracking system. Current estimates of the mean AIDS incubation time are available in the literature. Our model implies that the probability of infection per injection with a contaminated syringe equals 0.0067, which is slightly higher than the transmission probabilities of 1/300 to 1/200 estimated from needlestick studies, and a factor of 3 higher than estimates of the probability of HIV transmission per vaginal sex act from a infected man to an uninfected woman.


HIV testing and sexual behavior among intravenous drug users in Bangkok, Thailand. The relationships between previous HIV counseling and testing and sexual behavior were examined among injecting drug users in Bangkok. Six hundred one i.v. drug users (IVDUs) were recruited from drug treatment programs in November of 1989. A standardized interview on AIDS risk behavior was administered and a blood sample was collected for HIV testing of the 601 people. Fifty-six percent reported that they had not been previously tested (NPT), 15% had previously tested positive (PT+), and 29% had previously tested negative (PT-). Previous testing was associated with higher levels of safer sex and contraception with primary partners: 56% of the PT+ people with regular partners reported using condoms at least some of the time with that partner, compared with 28% of the PT- and only 20% of the NPT people. Similarly, 89% of the PT+ and 72% of the PT- people, compared with 59% of the NPT people, reported practicing some form of contraception with regular partners. The results strongly support the utility of HIV counseling and testing as a method of reducing heterosexual and perinatal HIV transmission among IVDUs in Bangkok.


Influence of HIV-1 infection and cigarette smoking on leukocyte profiles in homosexual men. The Multicenter AIDS Cohort Study. The interaction between the effects of HIV-1 infection and cigarette smoking on leukocyte profiles was studied in 307 HIV-1 seroconverters in the Multicenter AIDS Cohort Study (MACS). Longitudinal data for white blood cell (WBC) counts, WBC differentials, T cell subsets, and smoking behavior were collected semiannually for up to 7 years. Prior to seroconversion, total WBC count increased in direct proportion to daily cigarette consumption, but this effect disappeared within 3 years of seroconversion. Analyses of WBC subsets (lymphocytes, monocytes, and granulocytes) and lymphocyte subsets (CD4+, CD8+ and non-T[CD3-]) showed that smoking had only minor effects on the proportions of these cells. In contrast, HIV-1 seroconversion was associated with a dramatic decrease in CD4+ lymphocyte percentage, a large increase in CD8+ lymphocyte percentage, a small increase in total lymphocyte percentage, and small decreases in the non-T lymphocyte and granulocyte percentages. These findings indicate that the effect of smoking on CD4 cell counts is (a) nonspecific, (b) maximal in seronegative individuals; and (c) lost by 3 years after seroconversion. Although the mechanism of the loss of smoking-induced leukocytosis after seroconversion remains to be determined, our results suggest that the effects of smoking are not likely to be important in the clinical use of leukocyte measurements, including measurements of CD4 lymphocytes, in individuals who have been HIV-1 seropositive for more than 3 years.


National study of knowledge of AIDS, testing patterns, and self-assessed risk among health care workers. We conducted a study to assess the level of AIDS knowledge, testing behavior patterns, and self-assessed risk of contracting AIDS for a representative sample of health care workers in the United States. The study was based on data collected in the 1989 AIDS Knowledge and Attitudes Supplement to the National Health Interview Survey. Health care workers in four occupational groups were compared with other members of the labor force and with one another. The survey included 1,620 respondents identified as health care workers and 25,217 respondents with occupations other than in health care. Health care workers were more knowledgeable about AIDS than were other workers; approximately 55% and 25%, respectively, reported knowing a lot about AIDS. They were also more likely to have been tested (34%) than other workers (24%) and to have done so voluntarily (28% versus 14%). Health care workers also believed they had higher risk of contracting AIDS (8% versus 3%), although they were about equally likely to report being in one of the six high-risk groups. Among health care workers, those in the health diagnosing occupations were the most knowledgeable about AIDS (74% reported knowing a lot) and were the most likely to have been tested (41% were tested at least once). Health service workers were the least knowledgeable; only 38% reported knowing a lot about AIDS and only 26% reported being tested.


Racial misclassification of American Indians with AIDS in Los Angeles County. American Indian/Alaska Natives (AI/ANs) appear to be underrepresented in AIDS surveillance statistics. We estimated the accuracy of racial classification and reporting completeness of AIDS among AI/ANs in Los Angeles County by surveying community-based organizations (CBOs) that provide services to persons with AIDS and then comparing the survey to AIDS surveillance data. The surveyed CBOs reviewed 6,500 records and found 60 Native American (the classification used by CBOs for AI/ANs) clients with AIDS compared with six AI/AN AIDS cases reported to the Los Angeles County AIDS surveillance registry. Racial classification was evaluated for 37 (62%) of the 60 Native American CBO clients. Only 11 (30%) of the 37 were verified as AI/ANs. The remaining 26 (70%) misunderstood the racial nomenclature and were reclassified by the CBOs as other races. Of 10 verified AI/AN clients for whom names were available, eight (80%) had been reported to the AIDS registry. However, seven (88%) of these eight were erroneously reported as other races. Racial misclassification accounts for much of the underrepresentation of AI/ANs in the Los Angeles County AIDS surveillance registry.


The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC. The HIV Tat protein is able to upregulate the transcription by RNA polymerase III of cotransfected or endogenous cellular Alu-repeated sequences in both HeLa and Jurkat T cells. This effect is mediated by an increase in the activity of transcription factor TFIIIC, which binds to the B box in the RNA polymerase III Alu promoter. This is the first example of an effect of the Tat protein on the transcription of a cellular gene or on the activity of a cellular transcription factor. The significance of this effect for the life cycle of HIV and its interaction with infected cells is discussed.


Clonal dominance: cause for a limited and failing immune response to HIV-1 infection and vaccination. Oligoclonal and monoclonal antibody populations against different HIV-encoded proteins are common in sera from healthy HIV-1-infected individuals. This is especially important when it includes functional antibody repertoires directed at neutralizing cell free virus or inhibiting cell fusion of virus-infected cells. In the host, during the acute viral syndrome following HIV-1 infection, a rapidly replicating, cell-free and genotypically homogeneous viral population is known to arise from the transmitted viral inoculum. Dominant B and possibly T cell clones responsible for both functional and nonfunctional antibodies appear to arise early in response to this initially homogeneous cell-free viral population heralding seroconversion. During the viremic phase, deposition of cell-free virus as either complement coated or as immune complexes (iccosomes) within the germinal centers results in continued and long-term boosting of primed B cells. This saturation of antigen presenting germinal centers and the presence of limited, immunodominant cross-reactive epitopes on the envelope glycoprotein of the closely-related and immune selected viral quasispecies in the host appear to continue the boosting effect of the primed secondary response. This repertoire freeze appears to be responsible for limiting the recruitment of new uncommitted B cells to other functional epitopes or affinity maturation of B-cell clones to escape variants and the subsequent production and quality of functional antibody against the evolving/selected virus populations. This may include in addition to neutralizing and cell fusion inhibiting antibody, direct complement-fixing and/or NK-directed antibody-dependent cell-mediated antibody as well as various effector, helper, or T cell-mediated activity. In addition to antiviral antibody responses, antibody directed to other invading pathogens or opportunistic organisms may also be clonaly restricted. Antibody facilitating infectivity or blocking effective immunity may also be included in this phenomena and thus be over represented by such a mechanism. AIDS vaccines utilizing the envelope must identify these epitopes to avoid creating clonal dominance and therefore possibly limit the breadth and specificity of a humoral response following infection. Furthermore, immunotherapeutic approaches designed to recruit humoral immune effector function must be able to overcome the dominance of noneffective antibodies and restore a normal polyclonal immune response against HIV. Further research, therefore, into the humoral and cellular dysregulating properties of the HIV-1 envelope is warranted.


Report of a consensus workshop, Siena, Italy, January 17-18, 1992. Early diagnosis of HIV infection in infants. To promote progress in the research and development of early diagnostic tests for HIV in young children an international workshop was held on January 17-18, 1992, in Siena, Italy. Experts on pediatric AIDS, diagnostic retrovirology, and immunodiagnosis discussed and summarized the state-of-the-art and made recommendations for general application of several tests and further evaluation and continued research for other candidate tests. From the discussions it was clear that the field has advanced beyond the time when it was necessary to wait until the infant reached 18 months of age before attempting the diagnosis with conventional serologic tests for HIV. About half of infected infants can now be identified at birth, approximately 90% by 3 months of age, and almost all by 6 months of age using HIV culture and polymerase chain reaction assays. IgA antibody tests and p24 antigen tests have also proved useful, although they are not as sensitive in newborn infants. The fact that HIV can be detected in only one-half of infected infants at the time of birth points to the need for further research on the timing of transmission and the natural history of perinatally acquired HIV infection to understand the limitations of current early diagnostic tests and to develop new approaches to overcome these problems.


Uses and implications of the contextual approach to child custody decisions. Child custody litigation signals parental conflicts that have serious implications for a child's long-term development. The authors describe a family systems approach to child custody decision making--the contextual approach, derived from contextual family theory. A case study analysis and pilot study illustrate the use of the approach with a small group of families who turn to the legal system to resolve custody or visitation disputes. The findings suggest the approach's usefulness in helping families create alternatives to continued disputation. The findings also reinforce the need for further research to test the preventive potential of the approach in reducing returns to court.


In support of sibling inclusion: a literature review. The responses of siblings to a childhood mental illness have been conceptualized in different ways. When siblings have not been ignored, they have been viewed most frequently as an influence upon the illness or as subject to the same dynamics that were believed to have caused the mental illness. As conceptualizations of the causes of mental illness have changed, the literature on siblings has changed to focus on the impact of the illness on the sibling. How siblings and sibling relationships are conceptualized has important implications for clinical research and practice. More research is needed to understand the sibling experience in childhood mental illness. Clinicians can do more for the family if all of the family dynamics and responses to the illness are explored.


Difficulties with teens: can nursing consultation help? Child/youth problems and psychiatric hospitalizations are increasing. A literature review suggests that there is an increased need for more nurses with the knowledge and skills necessary to work in this specialty area. The review also suggests that providing psychiatric nursing consultation services is one way to help direct care staff to strengthen or develop these skills. The authors describe a consultation project that took place on a newly developed 15-bed adolescent program in a 30-bed private psychiatric hospital. They examine the effectiveness of consultation sessions, ascertained through both verbal and written evaluations of staff members. The outcome suggests that psychiatric nursing consultation services can be an important contribution in expanding the knowledge base of direct care staff (child care specialists and nurses) who work with the hospitalized adolescent psychiatric patient.


[Recent advances in the carbon-carbon bond forming reactions with alpha-chlorosulfides]. This review describes our recent studies on the carbon-carbon bond forming reactions of alpha-chlorosulfides with arenes, alkenes, and alkynes. Applications of these reactions to the synthesis of natural products are also presented.


[Asymmetric synthesis of nitrogen-containing biologically active compounds utilizing intramolecular aminocyclization to olefin of secondary allylic alcohols]. The progress of the asymmetric syntheses of nitrogen-containing biologically active compounds such as pyrrolidine, pyrrolizidine, indolizidine alkaloids, and unusual amino acids has been reviewed. Our recent advances in taking advantage of stereoselective aminocyclization of homochiral N-alkenyl urethanes and thioimitates containing allylic hydroxyl group have provided an attractive entry into the functionalized pyrrolidine skeletons as chiral building blocks. A promising approach to a number of biologically active compounds such as alkaloids has emerged.


[Protective effects of the bark of Myrica rubra Sieb. et Zucc. on experimental liver injuries]. The methanol extract from the bark of Myrica rubra SIEB. et ZUCC. showed protective effects on liver injuries induced by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) in rats. In this study, the fractions and some compounds from the bark of M. rubra were investigated for the protection against CCl4 inducing liver injuries in rats. The active principles for the protection were recognized in two fractions (M-3 and M-5 Fr. 1) obtained from the methanol extract, and one of the active principles in the fraction (M-3) was found to be myricanol 5-O-beta-D-(6'-O-galloyl)-glucopyranoside. In addition, these fractions protecting liver injuries induced by CCl4 showed significant protective effects against cholestasis induced by ANIT.


The Attending Nurse: a new role for the advanced clinician. The Attending Nurse Model as a unique role for the advanced practitioner was implemented and evaluated in an acute care psychiatric setting with an adolescent patient population. Program evaluation results demonstrated that the Attending Nurse role increased general satisfaction and role clarity while decreasing role tension. In addition, the role increased communication with patients' family members. Comparisons are made between the traditional primary nurse and the Attending Nurse roles.


[Subcellular distribution of porphyrins and anti-lipid peroxidative effect in protoporphyrin-administered rat liver]. The distribution and the anti-lipid peroxidative effects of porphyrins in the hepatic subcellular fractions in rats were studied after intravenous administration of protoporphyrin (PP). PP and/or PP-derived porphyrins were mainly distributed in the membrane-containing fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the liver homogenates of rats receiving a 20 mg/kg dose of PP. The lipid peroxidation induced by L-ascorbic acid in the fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the PP-treated rats was suppressed during 1-168 h, 1-168 h and 12-168 h, respectively, after the PP treatment. The suppression of the peroxidation in the liver mitochondria from the PP-treated rats was further enhanced by the addition of the hepatic cytosol from the PP-treated rats. The extent of the suppression by the addition of the cytosol from the PP-treated rats at 24 h after the PP administration was greater than those at 0 and 168 h after the PP administration. These results indicate that PP and/or PP-derived porphyrins distributed in the liver still exert antioxidative actions and that there might exist some unknown factors enhancing the actions in the hepatic cytosol.


[Effect of shikonin and its derivatives, pentaacetylated shikonin (MDS-004) on granuloma formation and delayed-type allergy in experimental animals]. Of twelve reduced and acetylated derivatives of shikonin, a chemical constituent of Shikon, the accelerating activity on granuloma formation and the inhibitory activity on delayed-type allergy were investigated in order to find a compound having more characteristic effect than shikonin on wound healing in experimental animals. As a result, it was found that a reduced and pentaacetylated derivative of shikonin, MDS-004, has more excellent pharmacological activity. MDS-004 (0.1-1 mg/pellet) accelerated dose-dependently felt-pellet-induced granuloma formation when given topically together with felt-pellets in rats. It also produced strong inhibition against delayed-type allergies (ear edema) caused by oxazolone and dinitrofluorobenzene by topical application of up to 1 mg/ear to the ear skin of mice; its potency was far superior to that of shikonin. Orally administered MDS-004, unlike shikonin, inhibited carrageenan-induced hind paw edema, and exhibited tendency to heal acetic acid-induced gastric ulcer in rats. However, MDS-004, as well as commercial wound healing drugs tested and shikonin, did not show any healing action in the incised and open wound models in rats, if applied topically to the wound as 5 and 10% powders. On the other hand, MDS-004 did not produce irritative action on the ear skin at a topical dose of 1 mg/ear different from shikonin, and any behavioral changes after oral administration of 100 mg/kg in mice. These results suggest that a white powder MDS-004, different from deep purple shikonin, has accelerating action on granuloma formation without irritative action and stronger inhibitory action on delayed-type allergy by topical application than shikonin.


[Determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma by ion-pair high-performance liquid chromatography]. A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma. This method was compared with other two methods, i.e. ion-suppression and phosphate buffer methods. Sennoside A was eluted without interference in this ion-pair method, while the determination of sennoside A was interfered by co-existing components in the other two methods.


[Pharmacological studies on leaf of Arctostaphylos uva-ursi (L.) Spreng. IV. Effect of 50% methanolic extract from Arctostaphylos uva-ursi (L.) Spreng. (bearberry leaf) on melanin synthesis]. Effects of 50% methanolic extract (U-ext) from the leaf of Arctostaphylos uva-ursi (L.) Spreng. (bearberry leaf) on melanin synthesis were investigated in vitro. The U-ext and arbutin isolated from the bearberry leaf had an inhibitory effect on tyrosinase activity. Furthermore, the U-ext inhibited the production of melanin from dopa by tyrosinase and from dopachrome by autoxidation. These results suggest that the bearberry leaf was found to be an effective inhibitor of the production of melanin.


[Molecular interaction in pharmaceutical solution, solubilization, partition, and stability of drugs]. The pharmaceutical studies carried out by the author during 40 years were reviewed from the viewpoint of molecular interaction. Included subjects are: electrostatic interaction between drug ions, ion pair formation and its partition to organic phase, drug solubilization by adjuvants, partition of drugs between aqueous and micellar phases, cyclodextrin inclusions, human serum albumin binding and drug stability related to the esterase-like activity of the albumin, and oral liposome preparation of vitamin K1. The drug stabilities related to those molecular interactions were emphasized.


[Development of multicomponent immunoassay and micro-localization analysis by laser-photoacoustic and microscopic image analyzer]. Laser photoacoustic spectroscopy (PAS) has a potential to be developed as a sensitive and solid-phase analytical method and was applied to enzyme immunoassay. The test sample for immunoassay was prepared by adsorbing multi-component immunoglobulins on a nitrocellulose membrane filter. Human lambda- and kappa-chains, which are used as a principal indication of malignant lymphoreticular disease, and immunoglobulin G were used as model proteins, and PAS immunoassay was applied to the individual detection of these three proteins in the urine. Furthermore, in order to develop a sensitive analysis for particular biological components in tissues or cells, laser photoacoustic microscopy (PAM) and video intensified microscopy (VIM) were developed. PAM was shown to be applicable to the detection and quantification of human lambda-chain in a micro-region of the tissue sections of the human fetal spleen and pancreas. VIM was applied to the detection of stimulation-response processes in a cell. By using neutrophils which are stimulated by many substances and produce active oxidants as the results, dynamic changes in the stimulation-response process in a living cell were visualized as fluorescence or chemiluminescence images by the VIM system.


[Determination of synephrine in oriental pharmaceutical decoctions containing Aurantii nobilis pericarpium by ion-pair high-performance liquid chromatography]. A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of synephrine in oriental pharmaceutical decoctions containing Aurantii Nobilis Pericarpium. An ODS column and a mixture of water, acetonitrile, sodium dodecyl sulfate and phosphoric acid (65:35:0.5:0.1) as a mobile phase were used for the separation. Synephrine was eluted without interference by other co-existing components within 15 min.


[Oxidation of hydrogen sulfide with cell-free extract of Hyphomicrobium neptunium ATCC 15444]. Soluble (Fr. 1) and membrane (Fr. 2) fractions were prepared from the cell-free extract of Hyphomicrobium neptunium ATCC 15444, and their effects on the oxidization of hydrogen sulfide (H2S) were studied. When H2S gas was supplied to Fr. 1 and Fr. 2, sulfur in both fractions and the majority of thiosulfate ion in Fr. 1 were detected. The sulfide-oxidizing activity in Fr. 2 but not in Fr. 1 was inhibited by the addition of diethyldithiocarbamate, suggesting that Fr. 1 and Fr. 2 have different types of sulfide-oxidase, and that Fr. 2 would include cytochrome c dependent sulfide oxidase. It was also found that thiosulfate ion was formed from sulfur and sulfite ion by adding Fr. 1. However, the pronase-treatment of Fr. 1 did not influence on the formation of thiosulfate ion. These results suggest that H2S was oxidized to sulfur and sulfite ion by two types of sulfide oxidase and sulfur oxidase in H. neptunium ATCC 15444, and that the sulfite ion changed rapidly to thiosulfate through a non-enzymatic reaction with sulfur.


[The mechanism of the renal excretion of disopyramide in rats. I]. The mechanism involved in the renal excretion of disopyramide (DPM) is still incompletely understood. The purpose of this study was to examine the renal handling of DPM and the interactions between DPM and several organic anionic or cationic drugs related to the renal tubular secretion, using the renal clearance and renal cortical slices uptake techniques in rats. The clearance ratio of DPM was greater than that of glomerular filtration and this suggests the tubular secretion of DPM. The clearance ratio of DPM did not change after infusion of either anionic drugs (p-aminohippurate and probenecid) or a cationic drug (cimetidine). The results of time and concentration-dependent experiments using renal cortical slices demonstrated that DPM was accumulated against a concentration gradient by a saturable process. Inhibition of uptake by 2,4-dinitrophenol and cyanide indicated an energy dependence. DPM uptake was considerably inhibited by the cationic drugs, cimetidine and quinine, suggesting that DPM was transported by the cation transport mechanism. Probenecid, a competitor for the anion transport mechanism, moderately inhibited DPM uptake.


[Limonoids in Phellodendron amurense (Kihada)]. Limonoids and their glucosides in the seeds and barks of Phellondendron amurense (Kihada) were analyzed. The seeds contained limonin (1950 ppm), obakunone (20 ppm), limonin 17-beta-D-glucopyranoside (820 ppm) and obakunone 17-beta-D-glucopyranoside (1360 ppm). The barks contained limonin (6760 ppm), obakunone (1240 ppm) and nomilin (270 ppm).


Binary combination effects of some pharmacologically active chemicals as promoters of tumorigenesis. Identification of potential interactions in exposures either to simultaneous or sequential combinations of carcinogenic chemicals and chemicals that modify carcinogenesis poses considerable difficulties in human health risk assessments. Studies of experimental carcinogenesis over the past four decades have revealed that many pharmacologically active agents possess tumorigenesis-promoting properties. The effort to identify the possible chemical structural basis of interactions of binary combinations of carcinogenic chemicals and chemical agents that modify carcinogenesis led to the identification of a class of structurally diverse and pharmacologically active tumorigenesis promoters that are known as pharmaceuticals. The chemical class-class interactions of carcinogens and pharmaceutical agents with reported tumorigenesis-promoting properties and the possible biochemical mechanism(s) that underlie such interactions are discussed.


Physiological modeling of disposition of potential tumor-imaging radiopharmaceuticals in tumor-bearing mice. Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc-labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radiopharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least-squares regression with MULTI-FORTE), and clearance terms (also determined by nonlinear least-squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1-3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor-imaging agents.


Release of polyionizable compounds from submicrometer oil-in-water emulsions. A novel, general, theoretical equation that describes the release of polyionizable compounds from submicrometer emulsions was derived and evaluated. The model accounts for simultaneous partitioning, interfacial activity, and adsorption to surfactant for n independent drug species and j surfactant species in a single emulsion system. Under the appropriate conditions, this model collapses to a previously described model for submicrometer emulsions. The model was tested for submicrometer emulsions containing a model dibasic compound (quinine sulfate). Drug release behavior was observed at pH 3.00, 5.07, and 7.50 in the presence and absence of an anionic surfactant (sodium lauryl sulfate). At each pH, the proposed theory describes the observed release behavior. At all pHs studied, a substantial amount of quinine was adsorbed to the surface of the oil droplet. Presumably, this behavior was largely the result of electrostatic attraction between ionized drug and sodium lauryl sulfate at the oil-water interface. Adsorption constants were evaluated for complexation of cationic and dicationic species of quinine to sodium lauryl sulfate, and the adsorption constant of the cationic species was larger, presumably because of the ionic nature of the surfactant.


Chloride-37 nuclear magnetic resonance spectroscopic study of binding of salicylic acid and other hydroxybenzoic acids to the band 3 anion transport protein of human erythrocytes. Chloride-37 nuclear magnetic resonance spectroscopy was used to investigate the displacement of chloride (Cl-) from binding sites on band 3 anion transport protein in human erythrocytes by salicylic acid and five other hydroxybenzoic acids (HAs). All the HAs studied displaced Cl- from these binding sites. The association constants for binding of the HAs to band 3 anion transport protein were larger than that for Cl- and dependent on the specific structural features of the molecule, rather than general physicochemical characteristics.


A kinetic study of the role of band 3 anion transport protein in the transport of salicylic acid and other hydroxybenzoic acids across the human erythrocyte membrane. The mechanism of transport of salicylic acid and five other hydroxybenzoic acids across the human erythrocyte membrane was investigated. The specific anion transport inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, reduced but did not totally abolish transport of these acids. This observation suggests that these acids are transported by two parallel processes, one involving the band 3 anion transport protein channel and the other probably involving passive diffusion of the un-ionized molecule. The activation energies for membrane transport were large (99-127 kJ.mol-1), an observation that is consistent with the rate-limiting step for anion transport being the conformational change of the band 3 anion transport protein.


Transport of drugs through human erythrocyte membranes: pH dependence of drug transport through labeled human erythrocytes in the presence of band 3 protein inhibitor. To reveal the role of the band 3 anion transport protein of the erythrocyte membrane in drug transport through the membrane, the possible effects of inhibitors of anion transport on the permeability of some anionic drugs were examined. The amounts of these drugs that permeated varied markedly with the pH of the outer medium around human erythrocytes that contained the band 3 protein inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In the pH range 7.0-8.0, the membrane permeability of drugs through DIDS-treated erythrocytes was affected by a slight pH change (0.2), whereas that through the intact erythrocytes was not pH dependent. These results suggest that the band 3 protein acts not only as a channel for the transport of anions or some anionic drugs but also as protection for the transport system from changes in the pH of the outer medium.


Pharmacokinetics of parenteral 13-cis-retinoic acid formulations in rats. The pharmacokinetics of three 13-cis-retinoic acid formulations were studied after intraperitoneal (ip) administration to rats. Rats were given ip injections of 2.5 mg of 13-cis-retinoic acid per 360 g of body weight; the drug was administered as an alkaline solution, suspended in corn oil, or as a mixture with polysorbate 80. The alkaline solution was also given intravenously (iv) via the tail vein as a control. The mean elimination rate constant, calculated from data from iv administration, was 0.72 +/- 0.088 h-1 (r = 0.988). The peak concentration in plasma and the time to reach this maximum were 14 mg/L and 0.5 h, 22 mg/L and 2 h, and 10 mg/L and 1 h for the drug administered as an alkaline solution, suspended in corn oil, and as a mixture with polysorbate 80, respectively. The areas under the concentration-time curve (concentration in plasma versus time) were 34.9 +/- 8.78 mg.h/L for the iv dose and 34.1 +/- 9.97, 62.4 +/- 32.3, and 25.9 +/- 12.0 mg.h/L for the ip doses of alkaline solution, suspension in oil, and mixture with polysorbate 80, respectively. Because of the rapid increase of concentration in plasma, which is identical to that of the iv profile, and the ease of its handling and preparation, the ip administered alkaline solution is the preferable formulation.


Anticonvulsant properties of some Mannich bases of conjugated arylidene ketones. Thirty 1-aryl-5-dimethylamino-1-penten-3-one hydrohalides and related compounds were prepared as candidate anticonvulsants and evaluated in maximal electroshock seizure (MES), subcutaneous pentylenetetrazole threshold, and neurotoxicity screens. Following administration by the intraperitoneal route, many of the compounds were active in the MES screen, whereas only 10% of the Mannich bases afforded protection in the subcutaneous pentylenetetrazole test. Quantitation of half of the compounds prepared revealed that many had activity comparable with that of clinically useful drugs in the MES screen. The anticonvulsant properties of eight of the compounds following oral administration were reduced considerably or abolished compared with those following intraperitoneal administration. Various synthetic strategies for future development of potential anticonvulsants are outlined.


Effects of cytochalasin, colchicine, and ethylenediaminetetraacetic acid on linoleic acid transport across rat jejunal enterocytes. The involvement and the site of interference of the cytoskeleton in the transport of linoleic acid across the rat jejunum was investigated by administration of microfilamentous and microtubular altering agents such as cytochalasin, colchicine, and ethylenediaminetetraacetic acid (EDTA). An isolated jejunal segment was perfused with a buffer containing labeled linoleic acid, and portal blood and perfusate samples were collected concomitantly at 5-min intervals and assayed for their radioactivity. At the end of the perfusion, the amount of radioactivity retained in the intestine was also determined. The results were analyzed by using a three-compartment physical model that allows the determination of mucosal and serosal permeability coefficients, from which changes in the permeability of the mucosal and serosal membranes were assessed. Cytochalasin decreased the permeability of the mucosal membrane to linoleic acid, but not that of the serosal membrane. The administration of colchicine, EDTA, or cytochalasin + colchicine increased the permeability of the serosal membrane but did not affect the mucosal membrane.


Pharmacokinetics and pharmacodynamics in the design of controlled-release beads with acetaminophen as model drug. Relationships between pharmacodynamics (drug concentration and effect) and pharmacokinetics were used to develop an oral, controlled-release-bead dosage form. Reported pharmacodynamic data were used with pharmacokinetic curves to identify effective therapeutic drug concentrations for optimum therapy for a drug with a "deep tissue" effective compartment. The commonly used, over-the-counter, non-narcotic, analgesic-antipyretic acetaminophen (APAP) was used as the model drug. Data reported in the literature were used to compare analgesic and antipyretic efficacy. Computer simulations were performed with MAXSIM (version 3.01) to suggest a zero-order drug release useful for a 12-h, oral, sustained-dosage form for antipyretic therapy in children, on the basis of current pediatric dosing of APAP. Coated APAP beads with the desired release rate were then developed with fluid-bed coating technology.


Cholinomimetic compound distinct from caffeine contained in coffee. II: Muscarinic actions. An extract with cholinergic activities was isolated from instant regular and decaffeinated coffees and purified. Intravenous injection of this cholinomimetic extract of coffee produced an abrupt depression in blood pressure and heart rate, changes that were distinct from those of known components of coffee, including caffeine, trigonelline, catechin, and chlorogenic acid. Pretreatment of the animals with naloxone, propranolol, isobutylmethylxanthine, hexamethonium bromide, and hemicholinium-3 chloride or bilateral vagotomy did not affect the cardiodepressive effects of the extract, whereas atropine completely abolished them. Direct injection of the cholinomimetic extract of coffee (20-100 micrograms) into the periaqueductal gray area of the midbrain did not produce any cardiovascular effect. However, the extract of coffee did cause relaxation of isolated rat and rabbit aortic ring preparations that were contracted under norepinephrine. The cholinomimetic extract did not inhibit purified acetylcholinesterase. This pharmacologic profile indicates that the cholinomimetic extract of coffee acts as a direct muscarinic agonist.


Effect of surfactants on release of a highly water-soluble medicinal compound from an inert, heterogeneous matrix. The release from a matrix compressed from a physical mixture of procaine hydrochloride, chlorinated poly(propylene), lactose, and a surfactant was investigated. With nonionic and cationic surfactants incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time, and as the concentration of the surfactants increased, the release was faster. When an anionic surfactant (sodium lauryl sulfate) was incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time; however, the release pattern depended on the concentration of the anionic surfactant. As the concentration of sodium lauryl sulfate increased to 4%, the release progressively slowed to a minimum because of the formation of a poorly soluble complex between the cationic procaine and the anionic surfactant. As the concentration of anionic surfactant increased further, the release increased as the complex was micellarly solubilized.