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PubMed2005

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: a nested case-control study in Shanghai, China.

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.

Adult↗
PubMed1994

Morphine-conditioned analgesia using a taste cue: dissociation of taste aversion and analgesia.

The present study examined the ability of a taste cue to serve as a conditioned stimulus (CS) for conditioning the analgesic effect of morphine. Rats were given three pairings of a taste CS with a morphine unconditioned stimulus (US). As expected, there was a decrease in CS intake across repeated pairings, indicating that a conditioned taste aversion was obtained. More important, presentation of the CS alone also increased paw-lick latencies on a hot plate test (either 50 degrees C or 54 degrees C hot plate), suggesting that an analgesic conditioned response (CR) was obtained. The dose of morphine required to produce conditioned analgesia was higher than the dose of morphine required to produce conditioned taste aversion. Using 15 mg/kg morphine, however, both conditioned taste aversion and conditioned analgesia were present when the morphine US was given immediately following CS intake, but not when given 6 h following CS intake. In contrast to morphine, pairing a taste CS with lithium produced a conditioned taste aversion without any conditioned analgesic response. These results indicate that acquisition of an analgesic CR is not the result of stress induced by an aversion to the taste CS.

Analgesia↗
PubMed2003

Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion.

RATIONALE: Latent inhibition (LI) describes a process by which repeated pre-exposure of a stimulus without any consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that LI is impaired in rats and in humans by injections of the indirect dopamine agonist amphetamine (AMPH), and that this disruption can be prevented by co-administration of either the typical neuroleptic haloperidol (HAL) or the atypical neuroleptic clozapine (CLZ). OBJECTIVES: Most of what is known of the pharmacology of LI is derived from studies using either the conditioned emotional response or the conditioned active avoidance paradigm. The goal of the present study was to determine whether these results would generalize to the conditioned taste aversion assay. METHODS: We tested whether AMPH (0.5 mg/kg) pretreatment would disrupt LI of a conditioned aversion to sucrose, and if so, which stage of the procedure is critical for mediating the disruption; in addition, we tested whether HAL (0.2 mg/kg) or CLZ (5.0 mg/kg) could restore such an expected LI disruption. RESULTS: We determined that AMPH disrupted LI when it was injected before pre-exposure and prior to conditioning, but not if the rats were injected before either stage alone. When HAL or CLZ was given 40 min before AMPH (before both pre-exposure and conditioning), it blocked LI disruption. CONCLUSION: These results are in line with the pharmacology of LI as derived from other conditioning paradigms. We conclude that the pharmacological regulation of LI in the CTA paradigm is similar to what has been observed previously in the conditioned emotional response and the conditioned active avoidance paradigms.

Adrenergic Agents↗
PubMed2003

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.

Administration, Oral↗
PubMed2002

Functional and structural analyses of trichloroethylene-degrading bacterial communities under different phenol-feeding conditions: laboratory experiments.

The effects of different phenol-feeding conditions on trichloroethylene (TCE) biodegradation and bacterial population structure in an aquifer soil community were studied. The soil sample, minerals, phenol, and TCE were mixed in glass bottles, which were then incubated under three different phenol-feeding conditions. First, phenol was supplied only once at 0.2 mM (condition 0.2P); second, it was added at 2.0 mM (condition 2.0P); and third, it was periodically supplied ten times at 0.2 mM (condition 0.2PS). TCE concentrations remained stable under conditions 0.2P and 2.0P. In contrast, TCE was completely degraded under condition 0.2PS. TCE/phenol-degrading bacteria were enumerated indirectly and functionally by quantitative PCR. The low- K(s) (half saturation constant) group of phenol-degrading bacteria, exhibiting high TCE-degrading activity, yielded a 50-fold higher population under condition 0.2PS than under condition 2.0P. The bacterial community structure under condition 0.2PS was studied by denaturing gradient gel electrophoresis targeting the genes encoding 16S rRNA and the largest subunit of multicomponent phenol hydroxylase. Sequence analysis of the major bands detected indicated the predominance of the low- K(s) group of TCE/phenol-degrading bacteria belonging to beta-Proteobacteria. These results suggest that continuous supplementation with phenol at a low concentration increases the population of the low- K(s) group of TCE/phenol-degrading bacteria.

Bacteria↗
PubMed2005

The association of child condition severity with family functioning and relationship with health care providers among children and youth with special health care needs in Alabama.

OBJECTIVE: The purpose of the present study is to assess how the severity of a child's condition affects family functioning and the relationship with health care providers among children with special health care needs in Alabama. METHODS: Using the data from the National Survey of Children with Special Health Care Needs (CSHCN), three variables were used as measures of condition severity: responses to the CSHCN screener questions, whether condition affected the ability to do things for children and youth with special health care needs (CYSHCN), and the level of severity of CYSHCN's condition. The dependent variables included family functioning and provider relationship. RESULTS: CYSHCN who only take prescription medicine for their chronic condition (MO) had lower condition severity from those who have other needs (NMO). In NMO CYSHCN, higher condition severity was associated with increased strain on family functioning outcomes and higher unmet needs in provider relationship outcomes, adjusted for demographic and insurance variables. Families of NMO CYSHCN with a more severe condition spent more temporal and financial resources and had a higher need for professional care coordination, and were less likely to have sensitive providers. CONCLUSIONS: Severity of condition is an important factor increasing strain on family resources and relationship with the provider. Our results indicate the need for professional care coordination and family support, particularly among those families in which there is a NMO CYSHCN with a more severe condition. This finding supports the mandate that all CYSHCN should have their health care coordinated and provided in the context of a medical home.

Adolescent↗
PubMed1990

The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect.

The aim of this study was to investigate the early period of neurite outgrowth in the regenerating rat sciatic nerve and to determine if the non-neuronal cells were important for the conditioning lesion effect. Regeneration distance was evaluated with the pinch-reflex test 6 h to 5 days after a test crush lesion. The regeneration velocity accelerated during approximately 3 days, whereupon outgrowth continued with a constant velocity. In unconditioned nerves the initial delay was 2.8 h and the constant rate of regeneration was 3.2 mm/day. In nerves with a distal conditioning lesion the initial delay was 2.4 h and the rate of regeneration increased by 52%. When the test crush was applied at the same place as the conditioning crush the initial delay was 1.9 h and the rate of regeneration increased by 61%. The conditioning lesion effect was not influenced by the distance between the cell body and the conditioning crush lesion. Furthermore, the conditioning lesion effect could not be expressed if conditioned axons grew into a freeze injured nerve section. Incorporation of [3H]thymidine increased in the regenerating nerve segment. The increase occurred earlier if this segment had been subjected to a conditioning crush lesion. The results of these experiments showed that peripheral neurites start to regenerate within a few hours after an injury, suggesting that growth cone formation is independent of the cell body reaction. A conditioning crush lesion increases the regeneration velocity and its acceleration, and the conditioning lesion effect cannot be expressed in the absence of living Schwann and other non-neuronal cells.

Animals↗
PubMedDate not supplied

Effects of social housing condition and behavior on growth of the Shionogi mouse mammary carcinoma.

We have demonstrated marked effects of social housing condition on the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma. The present study investigated the possible role of psychosocial variables in modulating the differential tumor growth rates observed. Male DD/S mice were reared individually housed (I) or in groups (G) of three or five siblings or nonsiblings. Following tumor cell injection, mice either remained in their rearing conditions (II, GG) or were rehoused (IG, GI). Effects of group size, sibling relationship, dominance status, change vs. no change in housing condition, and direction of change (individual to group or group to individual) were examined. Home cage behaviors were monitored both prior to and following tumor cell injection and rehousing. Overall, mice in the GI conditions showed faster tumor growth rates than mice in the IG conditions. Mice in the II and GG conditions showed intermediate tumor growth rates. Differences in group size and sibling relationship prior to and following tumor cell injection and rehousing had no significant influence on tumor growth rates. However, both change in housing condition and direction of change following tumor cell injection/rehousing were significant variables in modulating differential tumor growth rates. Dominance status differentially influenced tumor growth depending on whether mice experienced a change in housing; in the IG conditions, dominant mice showed faster tumor growth whereas in the GG conditions, dominant mice showed slower tumor growth than subordinate mice. Increased fighting among mice in IG compared to mice in GG conditions may play a role in modulating differential tumor growth rates.

Aggression↗
PubMed2006

The probability of causal conditionals.

Conditionals in natural language are central to reasoning and decision making. A theoretical proposal called the Ramsey test implies the conditional probability hypothesis: that the subjective probability of a natural language conditional, P(if p then q), is the conditional subjective probability, P(q/p). We report three experiments on causal indicative conditionals and related counterfactuals that support this hypothesis. We measured the probabilities people assigned to truth table cases, P(pq), P(p notq), P( notpq) and P( notp notq). From these ratings, we computed three independent predictors, P(p), P(q/p) and P(q/ notp), that we then entered into a regression equation with judged P(if p then q) as the dependent variable. In line with the conditional probability hypothesis, P(q/p) was by far the strongest predictor in our experiments. This result is inconsistent with the claim that causal conditionals are the material conditionals of elementary logic. Instead, it supports the Ramsey test hypothesis, implying that common processes underlie the use of conditionals in reasoning and judgments of conditional probability in decision making.

Analysis of Variance↗
PubMed2004

Hormonal status and test condition, but not sexual experience, modulate partner preference in female rats.

A series of experiments was conducted to determine the contributions of hormonal status, test condition, and sexual experience to the display of partner preference by female rats. Preference for a sexually active male rat over a sexually receptive female rat was assessed in independent groups of female rats tested in a condition limiting physical contact (No Contact) and a condition allowing for sexual interaction (Contact). Although hormonal status and test condition influenced the preference for a sexually active male, repeated testing and sexual experience had no effect. Experiment 1 demonstrated that independent of test condition, preference for the male is stronger in estrogen- and progesterone-primed rats than in rats receiving the vehicle. Moreover, independent of hormone condition, rats tested in the No Contact condition exhibit a stronger preference for the male than rats tested in the Contact condition, reflecting in part the active pacing of mating stimulation by sexually receptive rats tested in the Contact condition. Experiment 2 showed that the overall pattern of partner preference in proestrous and diestrous rats was similar to that observed in ovariectomized, estrogen- and progesterone-primed, and oil-treated rats, respectively. In Experiment 3, rats primed with estrogen alone did not exhibit a preference for the male even though fully receptive. Experiments 4 and 5 demonstrated that sexual experience does not affect the expression of preference for the male in estrogen- and progesterone-primed rats. The present findings demonstrate that the female rat's preference for the male is stable across repeated tests and is not affected by sexual experience. Our results also confirm that gonadal hormones influence the expression of a preference for a sexually active male versus a sexually receptive female and demonstrate that the magnitude of preference is modulated by test conditions.

Animals↗
PubMed2002

Comparative study of the linear solvation energy relationship, linear solvent strength theory, and typical-conditions model for retention prediction in reversed-phase liquid chromatography.

This paper describes two new retention models for predicting retention under different reversed-phase liquid chromatography (RPLC) conditions. The first one is a global linear solvation energy relationship (LSER) that expresses retention as a function of both solute LSER descriptors and mobile phase composition. The second is a so-called "typical-conditions model" that expresses retention under a given chromatographic condition as a linear function of retention under different so-called "typical" conditions. The global LSER was derived by combining the local LSER model and the linear solvent strength theory (LSST) of RPLC. Compared to local LSER and the LSST models, the global LSER model requires far fewer retention measurements for calibrating the model when different solutes and different mobile phase compositions are involved. Its fitting performance is equal to the local LSER model but worse than that of LSST. The poor fit of the global LSER results primarily from the local LSER model and not from the LSST model. The typical-conditions model (TCM) was developed based on a concept of multivariate space that is conceptually compatible with LSER. However, no LSER descriptors are used in the TCM approach. The number of input conditions needed in the typical-conditions model is determined by the chemical diversity of the solutes and the conditions involved. Principal component analysis (PCA) and iterative key set factor analysis (IKSFA) were used to find the number of typical conditions needed for a given data set. Compared to LSER, LSST, and global LSER, the typical-conditions model is more precise and requires fewer retention measurements for calibrating the model when different solutes and different stationary and/or mobile phases are involved.

Chromatography, Liquid↗
PubMedDate not supplied

The effects of fluency-evoking conditions on voicing onset types in persons who do and do not stutter.

Voicing onset changes between control conditions and three fluency-evoking conditions (choral reading [CHORAL], delayed auditory feedback [DAF], and noise [NOISE]) were studied in 12 persons who do not stutter and 10 who do stutter. Voicing onsets were distinguished physiologically using airflow prior to voicing, with zero airflow prevoicing categorized as hard and the rest as breathy. Persons who stutter were more fluent under all fluency-evoking conditions than control conditions. Speaking under fluency-evoking conditions did not significantly increase the overall proportion of breathy onsets from control conditions for either group. However, looking only at hard onsets in the control condition, we found that both groups changed significantly more to breathy (p = 0.001) under CHORAL and NOISE. In persons who stutter, onset type was not associated with whether a word was produced fluently or dysfluently in the control condition. Also, no relationship was found between onsets changing to breathy under fluency-evoking conditions and onsets changing to fluent. The results suggest that although fluency-evoking conditions can modify some voicing onset behaviors, these modifications do not relate to improvements in fluency.

Adult↗
PubMed2003

Effects of body condition score and score change on the reproductive performance of dairy cows: a meta-analysis.

A meta-analysis was conducted to evaluate the effects of body condition score (BCS) at parturition and at first AI, and of body condition change during the early lactation period on the variables pregnancy rate at first AI and number of days open in dairy cattle. Inclusion criteria for the publications were: comparison of at least two groups of animals of different categories of BCS or change (independent variables) and consideration of pregnancy rate at first AI or number of days open (dependent variables). Fifteen papers were selected and 23 excluded. Data corresponding to 7733 cows from 11 studies described in 10 papers were included in the analysis of pregnancy rate at first AI, and those derived from 4529 cows from 11 studies described in 10 papers were used to analyze effects on the number of days open. Analyses were stratified according to study design and milk production characteristics. We defined low, intermediate and high categories of BCS for values lower than 2.5, from 2.5 to 3.5, or higher than 3.5, respectively. The categories of body condition change were increase (gain in score), slight loss (0-0.5 point loss), moderate loss (0.6-1 point loss), and severe loss (over 1 unit loss). Intermediate body condition at parturition and at first AI, and a slight loss during the early lactation period were used as reference categories. The effects of body condition on the variable pregnancy rate at first AI were highly heterogeneous, while all the studies considering the number of days open presented homogeneous results. A clear association between body condition category and pregnancy rate at first AI was detected only when the effect of a low score at parturition was analyzed: pregnancy rate at first AI significantly decreased by about 10% in cows delivering in poor condition. Animals with a high BCS at parturition showed a significant reduction in the number of days open of 5.8 or 11.7 when compared with animals with an intermediate or low body condition, respectively. In animals in the high body condition category at first AI, the variable days open showed a significant drop of 11.9 or 24.1, compared to animals in the intermediate or low categories, respectively. A severe loss in score during early lactation was related to a significant (10.6) increase in the number of days open, while a slight or moderate body condition change, either loss or gain in score, was not significantly related to the variable days open. We found that the number of days open was a good indicator of the effects of BCS or change in score on reproductive performance in dairy cattle. The variable pregnancy rate at first AI, however, yielded heterogeneous results among studies.

Analysis of Variance↗
PubMed2002

The meninges contribute to the conditioned taste avoidance induced by neural cooling in male rats.

After consumption of a novel sucrose solution, temporary cooling of neural areas that mediate conditioned taste avoidance can itself induce conditioned avoidance to the sucrose. It has been suggested that this effect is either a result of inactivation of neurons in these areas or of cooling the meninges. In a series of studies, we demonstrated that cooling the outer layer of the meninges, the dura mater, does not contribute to the conditioned taste avoidance induced by cooling any of these areas. The present experiments were designed to determine whether the inner layers of the meninges are involved. If they are involved, then one would expect that cooling locations in the brain that do not mediate conditioned taste avoidance, such as the caudate putamen (CP), would induce conditioned taste avoidance as long as the meninges were cooled as well. One also would expect that cooling neural tissue without cooling the meninges would reduce the strength of the conditioned taste avoidance. Experiment 1 established that the temperature of the neural tissue and meninges around the cold probes implanted in the CP were cooled to temperatures that have been shown to block synaptic transmission. Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex and meninges induced conditioned taste avoidance. In experiment 3, a circle of meninges was cut away so that the caudate putamen and overlying cortex could be cooled without cooling the meninges. The strength of the conditioned taste avoidance was substantially reduced, but it was not entirely eliminated. These data support the hypothesis that cooling the meninges contributes to the conditioned taste avoidance induced by neural cooling. They also allow the possibility that neural inactivation produces physiological changes that can induce conditioned taste avoidance.

Animals↗
PubMedDate not supplied

How do prudent laypeople define an emergency medical condition?

To determine the public's perception as to the general definition of an emergency medical condition (EMC), and to compare opinions between the general public and healthcare workers (HCW) on which specific medical conditions require emergency department (ED) care, a survey of people at 12 supermarkets and shopping malls in Northern California was conducted over a 6-month period in 1997. Individuals over age 18 were asked in person to complete a survey sheet. It asked participants to choose one of four definitions of "emergency medical condition." In addition, people were asked to determine which of 30 chief complaints they thought needed care in the ED. Demographic information was also collected. A second set of surveys asking the same questions was conducted among nonemergency healthcare providers at hospitals. Healthcare worker was defined as an MD, RN, LVN, or PA. A total of 1,018 members of the public and 126 healthcare workers completed the survey. EMC definitions selected by the public were: 1) an abbreviated federal EMTALA definition: a condition that may result in death, permanent disability, or severe pain (48.7%); 2) the federal definition plus other conditions preventing work (3.0%); 3) the federal definition plus any other conditions outside business hours (16.5%); and 4) any condition at any time as determined by the patient (31.6%). HCWs selected the following: definition 1 (71%); definitions 2 and 3 (0%); and definition 4 (27%). Definitions 1 and 3 were statistically different when comparisons were made between the public and HCWs. On the question of which of the 30 chief complaints needed care in an ED, agreement was seen between the public and HCWs for severe abdominal pain (94% vs. 99%, respectively) and severe chest pain (96% vs. 99%, respectively). However, the two disagreed on the need for ED care for severe headache (58% vs. 91%, respectively); mild chest pain (51% vs. 79%, respectively); and difficulty breathing (77% vs. 98%, respectively). No significant difference in opinions on the need for ED care was seen for some minor conditions: mild headache, sore throat, cough, flu symptoms, minor foot problems. No significant differences in answers occurred when age groups, occupations, or locations were compared. In conclusion, the public has split views concerning the general definition of an emergency medical condition. Approximately half uses a conservative federal definition, and half uses patient self-determined need as the definition. Data on which specific conditions need ED care provide additional insight on agreement between the public and HCWs on most problems. Both groups agree that many perceived minor medical complaints do not require ED care.

Adult↗
PubMed1999

Effect of exercise on hemodynamic conditions in the abdominal aorta.

PURPOSE: The beneficial effect of exercise in the retardation of the progression of cardiovascular disease is hypothesized to be caused, at least in part, by the elimination of adverse hemodynamic conditions, including flow recirculation and low wall shear stress. In vitro and in vivo investigations have provided qualitative and limited quantitative information on flow patterns in the abdominal aorta and on the effect of exercise on the elimination of adverse hemodynamic conditions. We used computational fluid mechanics methods to examine the effects of simulated exercise on hemodynamic conditions in an idealized model of the human abdominal aorta. METHODS: A three-dimensional computer model of a healthy human abdominal aorta was created to simulate pulsatile aortic blood flow under conditions of rest and graded exercise. Flow velocity patterns and wall shear stress were computed in the lesion-prone infrarenal aorta, and the effects of exercise were determined. RESULTS: A recirculation zone was observed to form along the posterior wall of the aorta immediately distal to the renal vessels under resting conditions. Low time-averaged wall shear stress was present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. Shear stress temporal oscillations, as measured with an oscillatory shear index, were elevated in these regions. Under simulated light exercise conditions, a region of low wall shear stress and high oscillatory shear index remained along the posterior wall immediately distal to the renal arteries. Under simulated moderate exercise conditions, all the regions of low wall shear stress and high oscillatory shear index were eliminated. CONCLUSION: This numeric investigation provided detailed quantitative data on the effect of exercise on hemodynamic conditions in the abdominal aorta. Our results indicated that moderate levels of lower limb exercise are necessary to eliminate the flow reversal and regions of low wall shear stress in the abdominal aorta that exist under resting conditions. The lack of flow reversal and increased wall shear stress during exercise suggest a mechanism by which exercise may promote arterial health, namely with the elimination of adverse hemodynamic conditions.

Aorta, Abdominal↗
PubMed1999

Clozapine-induced potentiation of latent inhibition is due to its action in the conditioning stage: implications for the mechanism of action of antipsychotic drugs.

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its non-reinforced pre- exposure. LI is impaired in some subsets of schizophrenic patients and in rats treated with amphetamine. Antipsychotic drugs (APDs) potentiate LI under conditions that are insufficient to produce LI in control animals, namely, low number of pre-exposures or high number of conditioning trials. The present experiments tested the proposition that LI potentiation under both conditions stems from the action of APDs in the conditioning stage. Experiments 1-3 used 10 pre-exposures and 2 conditioning trials, and tested the effects of 2.5, 5, and 10 mg/kg clozapine, respectively. Experiments 4-6 used 40 pre-exposures and 5 conditioning trials, with clozapine doses as above. Clozapine was administered in either the pre-exposure, the conditioning stage, or in both. In all the experiments, vehicle controls did not show LI. Overall, clozapine administration in conditioning, irrespective of drug condition in pre-exposure, produced LI. The implications of these results for the mechanism of action of antipsychotic drugs are discussed.

Journal Article↗
PubMedDate not supplied

Effect of simultaneous application of stressful culture conditions on specific productivity and heterogeneity of erythropoietin in Chinese hamster ovary cells.

A single stressful culture condition induced by hypoosmotic stress (210 mOsm kg(-1)), low culture temperature (32 degrees C), or NaBu addition (1 mM) resulted in a 1.8- to 2.2-fold enhancement of specific erythropoietin (EPO) productivity (qEPO) of recombinant Chinese hamster ovary (rCHO) cells compared to normal culture condition (37 degrees C and 310 mOsm kg(-1)). Simultaneous application of these stressful conditions further enhanced qEPO up to approximately 5-fold. However, the quality of EPO was affected by stressful culture conditions. The proportion of acidic isoforms of EPO under a single stressful condition was 2.8-13.8% lower than that under normal culture condition. Simultaneous application of the stressful conditions further decreased the portion of acidic isoforms but not significantly. Despite 5-fold enhancement of q(EPO), the portion of acidic isoforms under the simultaneous application of stressful culture conditions was 12.9-21.6% lower than that under normal culture condition. Taken together, these results suggest the potential of simultaneous application of different stressful culture conditions to the production phase of two-stage culture, where cell growth and production phases are separated, for improved EPO production.

Animals↗