Which foreign vaccine should the government purchase in a pandemic? Evidence from a survey experiment in the United States.

BACKGROUND: For many countries confronting a future pandemic, the initial vaccines available will come from abroad. Public hesitancy to receive these foreign vaccines is important, as it may create an incentive for governments to forego procuring them for public use. We investigate the influence of the vaccine's country of origin on public support for government procurement during the early stages of a pandemic and examine whether endorsements from the WHO can mitigate such biases. METHODS: In the summer of 2023, we carried out a survey experiment of 1,110 U.S. residents where we asked respondents to rate their support for vaccine purchasing policies for 20 hypothetical vaccines (13,320 evaluations). We varied the vaccine's country of origin and its endorsement status from the WHO, while also randomizing other vaccine attributes. RESULTS: Compared to foreign vaccines from countries Americans see favorable (e.g., Germany, the United Kingdom), those originating from less favorable countries (e.g., China, Russia), garnered lower support for government procurement. Our causal mediation analysis indicates that this country-of-origin effect is primarily driven by participants' sentiments toward the vaccine. Surprisingly, WHO endorsement does little to mitigate the effect of the vaccine's country of origin. These findings are consistent across various sample subsets and considerations of vaccine quality. CONCLUSION: Our study advances previous work on vaccine country-of-origin effects by assessing its impact on policy preferences for procuring initial vaccines from overseas (as opposed to uptake intentions), identifying a mechanism by which vaccine favoritism occurs, and documenting that neither personal disease susceptibility nor vaccine quality fully mitigates country of origin effects. We conclude by discussing why the study of "vaccine diplomacy" ought to not only include interstate dynamics governing vaccine purchasing and availability but also consider vaccine-producing countries' more general reputations.

Investigating how historical legacies of militarized violence can motivate COVID-19 vaccine hesitancy: Evidence from global dyadic survey.

BACKGROUND: In almost all countries, COVID-19 vaccines available for public use are produced outside of that country. Consistent with recent social science research, we hypothesize that legacies of violent conflict from vaccine-producing against vaccine-consuming countries may motivate vaccine hesitancy among people in targeted countries that purchase vaccines produced by the erstwhile aggressor. METHODS: Our analyses draw on data from the Correlates of War project and a large, representative survey of 18,291 adults that asked respondents in 16 countries to self-report their attitudes toward COVID-19 vaccines originating from 12 potential vaccine-producing countries in December 2020 (184 country-pairs, 208,422 ratings). For the main analysis, we used random-effect linear probability models and turned to Bayesian Model Averaging to probe the robustness of the main findings. RESULTS: We demonstrate that elevated levels of historical violence between vaccine-producing and vaccine-consuming countries are associated with increased negative feelings toward a COVID-19 vaccine produced by the vaccine producer. CONCLUSION: Global vaccine hesitancy may result, at least in part, from public perceptions of historical conflict between vaccine-producing and vaccine-consuming countries. These results can help public health practitioners better preempt and adjust for cross-national vaccine resistance.

Vaccine hesitancy, state bias, and Covid-19: Evidence from a survey experiment using Phase-3 results announcement by BioNTech and Pfizer.

BACKGROUND: Past survey studies document that people strongly prefer Covid-19 vaccines developed domestically over those developed abroad. Available evidence suggests that this preference for domestic vaccines over foreign ones may stem from prejudice against foreign countries, but identifying prejudice-based vaccine preferences is difficult because people also draw inferences about the quality of vaccines based on country of origin. We exploit a unique opportunity provided by the announcement of a viable vaccine by a bi-national venture, BioNTech and Pfizer, to examine the effect of such prejudice on vaccination intentions while controlling for beliefs about the vaccine quality. METHODS: We implemented a survey experiment in Germany and the United States (n = 582, 661 respectively) a few days after the BioNTech/Pfizer announcement of a viable vaccine. We randomized the identified company (and country) responsible for the vaccine development between BioNTech (Germany) and Pfizer (U.S.) and asked respondents when they would take said vaccine. RESULTS: In either the German and U.S. samples, we find little evidence that a country of origin of the vaccine makes a difference in when respondents intend to get vaccinated. We also see no evidence that those with a general animus toward the other foreign country would be more biased against a foreign vaccine. CONCLUSION: Our findings suggest that prejudice against foreign countries may be less of a concern for vaccine hesitancy and that its effect may be highly context specific.

Public support for development aid during the COVID-19 pandemic.

Global pandemics are a serious concern for developing countries, perhaps particularly when the same pandemic also affects donors of development aid. During crises at home, donors often cut aid, which would have grave ramifications for developing countries with poor public health capacity during a time of increased demand for health care. Because the major donors are democracies, whether they renege on promises would depend intimately on how donor citizens respond to the specific crisis. We conduct two survey experiments with 887 U.S. residents to examine how the 2020 COVID-19 pandemic influences their attitudes toward aid. We demonstrate that people's concern about the impact of COVID-19 on their country's financial situation reduces their support for aid. If they think that aid can help curb the next wave of the disease at home by first alleviating its impact in developing countries, people become substantially more supportive of giving aid. In contrast, merely stressing how COVID-19 might ravage developing countries barely changes their aid attitudes. Our findings have implications for what to expect from donors during global pandemics as well as how advocates may prevent aid from being cut.

Magnification Effect of Foveal Avascular Zone Measurement Using Optical Coherence Tomography Angiography.

PURPOSE: The aim of this study was to evaluate the foveal avascular zone (FAZ) of healthy subjects and examine the magnification effect. METHODS: A total of 33 healthy volunteers were enrolled and all subjects were eligible for analysis. Optical coherence tomography angiography (OCTA) examination scanned 3 × 3 mm of the macular area. The FAZ area was measured on the superficial OCTA en face image with and without correction by axial length. The relationship between changes in the FAZ area after correction with the axial length was examined. RESULTS: The mean age was 21.9 ± 0.6 years. The mean axial length was 24.87 ± 1.17 mm and mean spherical equivalent (SE) value was -3.64 ± 2.83 diopters (D). The FAZ area was 0.26 ± 0.10 mm2 before the axial length correction and 0.27 ± 0.10 mm2 after the correction. In the eyes that had an axial length longer than or equal to 26 mm or SE less than or equal to -6 D, the FAZ area after correction was significantly larger than that before correction (p < 0.01). The change of FAZ area after correction with axial length was significantly correlated with the axial length (R 2 = 0.88, p < 0.01) or SE value (R 2 = 0.55, p < 0.01). CONCLUSION: FAZ areas were comparable to previous reports. In high myopic cases, the magnification effect needs to be considered when evaluating the FAZ area.

Cortisol production in preterm infants with or without late-onset adrenal insufficiency of prematurity: A prospective observational study.

BACKGROUND: Immature adrenocortical function in preterm infants may cause inadequate production of cortisol under stress, resulting in adrenal insufficiency of prematurity (AOP). The objective of this study is to compare cortisol production in preterm infants with and without late-onset AOP. METHODS: Of 27 preterm infants born at less than 32 weeks gestation, cortisol production was analyzed in those who did (patients, group P) and did not (controls, group C) eventually develop late-onset AOP. Blood samples were prospectively collected every two weeks after birth, and steroid hormone concentrations in the pathway to cortisol production were measured retrospectively. RESULTS: We restricted the initial subjects to infants with gestation less than 29 weeks to adjust for confounding factors, culminating in matched infants in groups P (n = 8) and C (n = 11). The cortisol concentrations did not differ between the groups before AOP onset (P = 0.20), but the total concentrations of precursors for cortisol were higher in group P (P < 0.0001). The total concentrations of precursors in group C were inversely correlated with postmenstrual age (ρ = -0.38, P < 0.01). The pattern of changes in total concentrations of precursors differed between the groups (P < 0.05). CONCLUSION: Adrenal cortex maturity in preterm infants develops in parallel with postmenstrual age. Infants with late-onset AOP have undeveloped maturation of adrenocortical function after birth. CLINICAL TRIAL REGISTRATION: UMIN000022453.

Effects of Mathematical Analysis of Test Injection on the CT Value Estimation of the Aorta.

The circulation time and the mechanical acceleration time (MA time) of an automatic injector were simulated using pharmacokinetic analysis. The addition method and transfer-function method, which are mathematical techniques used for analyzing the test bolus method in multi-detector computed tomography, were used to verify the accuracy of estimation of the time-enhancement curve (TEC) of the main bolus. The TEC estimated using the addition method, and the TEC of the main bolus matched completely only if the MA time of the automatic injector was set to 0 seconds. Moreover, the estimation accuracy of the TEC deteriorated when the MA time was set according to the TEC estimated by the addition method. In contrast, the TEC estimated using the transfer-function method, except when the MA time of the automatic injector was 0 seconds, had higher accuracy than the TEC estimated using the addition method. In this study, the addition method, a number of additions of TEC, and MA time of the automatic injector were found to have a negative effect on the estimation accuracy of the main bolus. The use of the transfer-function method for determining the TEC and the MA time has a positive effect on the estimation accuracy of the main bolus.

[Isotropic Evaluation of Streak Artifact Using Extreme Value Statistical Analysis].

Previous studies have shown that extreme value statistics are useful for quantitative evaluations of streak artifacts on multi-detector computed tomography (MDCT). However, we hypothesized that the scanning direction of the extreme value would affect the quantitative value obtained using the conventional method. In this study, we developed the region of interest rotation method and calculating the extreme value, and we investigated the usefulness of this method in comparison with the conventional approach. For our examination, the high absorber was placed around a water phantom and a head and chest phantom. In the new method, linearity was confirmed in the Gumbel plot of all the phantoms. On the other hand, the value of the location parameter was significantly different according to the scanning direction with the conventional method. In conclusion, compared to the conventional method, the isotropic method of evaluation does not depend on the direction of streak artifact occurrence in the new method.

Genistein inhibits glucocorticoid amplification in adipose tissue by suppression of 11ß-hydroxysteroid dehydrogenase type 1.

Excess glucocorticoids promote visceral obesity, hyperlipidemia, and insulin resistance. The main regulator of intracellular glucocorticoid levels is 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive glucocorticoids into bioactive forms such as cortisol in humans and corticosterone in rodents. Hexose-6-phosphate dehydrogenase (H6PD), which is colocalized with 11ß-HSD1 in the intralumen of the endoplasmic reticulum, supplies a crucial coenzyme, NADPH, for full reductase activity of 11ß-HSD1. Therefore, it is possible that inhibition of 11ß-HSD1 will become a considerable medical treatment for metabolic diseases including obesity and diabetes. Genistein, a soy isoflavone, has received attention for its therapeutic potential for obesity, diabetes, and cardiovascular disease, and has been proposed as a promising compound for the treatment of metabolic disorders. However, the mechanisms underlying the pleiotropic anti-obesity effects of genistein have not been fully clarified. Here, we demonstrate that genistein was able to inhibit 11ß-HSD1 and H6PD activities within 10 or 20min, in dose- and time-dependent manners. Inhibition of 11ß-HSD2 activity was not observed in rat kidney microsomes. The inhibition was not reversed by two estrogen receptor antagonists, tamoxifen and ICI182,780. A kinetic study revealed that genistein acted as a non-competitive inhibitor of 11ß-HSD1, and its apparent Km value for 11-dehydrocorticosterone was 0.5µM. Genistein also acted as a non-competitive inhibitor of H6PD, and its apparent Km values for G6P and NADP were 0.9 and 3.3µM, respectively. These results suggest that genistein may exert its inhibitory effect by interacting with these enzymes.

Resveratrol inhibits 11ß-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes.

It has been suggested that resveratrol, a polyphenol in wine, can regulate adiposity because it decreases adipose deposition in mice and rats; however, the mechanism underlying this effect has not been fully clarified. In humans and rodents, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is expressed in liver and adipose tissue. 11ß-HSD1 converts inactive glucocorticoid into active glucocorticoid in adipocytes. Activated glucocorticoid plays an important role in the pathogenesis of central obesity. The objective of this study was to investigate the effects of resveratrol on 11ß-HSD1 activity in rodent adipose tissue. 11ß-HSD1 activity in microsomes from rat mesenteric adipose depots and 3T3-L1 adipocytes was determined in the presence of 11-dehydrocorticosterone with or without varying concentrations of resveratrol. Significant inhibition of 11ß-HSD1 by resveratrol was observed in rat adipose microsomes and 3T3-L1 adipocytes within 10 min. Time- and dose-dependent effects were also observed. The 11ß-HSD1 activity by resveratrol was also inhibited in rat epididymal adipose tissue, and this inhibition was not recovered by estrogen receptor blockers. The kinetic study revealed that resveratrol acted as a non-competitive inhibitor of 11ß-HSD1. Ki and IC50 values of resveratrol were 39.6 and 35.2 µM respectively. Further, resveratrol did not affect the activities of 11ß-HSD2 and hexose-6-phosphate dehydrogenase. These results suggest that the most likely mechanism of 11ß-HSD1 inhibition by resveratrol is via interaction between resveratrol and 11ß-HSD1 enzyme, rather than via a transcriptional pathway. We demonstrated that the antiobesity effects of resveratrol may partially be attributed to the inhibition of 11ß-HSD1 activity in adipocytes.

Involvement of the sigma1 receptor in the antidepressant-like effects of fluvoxamine in the forced swimming test in comparison with the effects elicited by paroxetine.

We studied the involvement of the sigma(1) receptor in the antidepressant-like effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in DBA/2 mice using the forced swimming test. The effects of the selective sigma(1) receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD1047) at 1mg/kg significantly antagonized the anti-immobility elicited by fluvoxamine (10mg/kg). However, the anti-immobility effects elicited by another SSRI, paroxetine (5m/kg), were not altered by BD1047. The selective sigma(1) receptor agonist 2S-(2α,6α,11R(*))-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol ((+)SKF-10047) elicited dose-dependent anti-immobility effects in DBA/2 mice. BD1047 significantly blocked the anti-immobility effects induced by (+)SKF-10047 at 10mg/kg. These results suggested that the sigma(1) receptor was associated with fluvoxamine-induced antidepressant-like effects but not with paroxetine-induced antidepressant-like effects.

Benzofuran derivatives inhibit 11ß-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissue.

Excess glucocorticoids promote visceral obesity and insulin resistance. The main regulator of intracellular glucocorticoid levels are 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive glucocorticoid into bioactive glucocorticoid such as cortisol in humans and corticosterone in rodents; therefore, the inhibition of 11ß-HSD1 has considerable therapeutic potential for metabolic diseases including obesity and diabetes. Benzofuran is a key structure in many biologically active compounds such as benzbromarone, malibatol A and (+)-liphagal. The aim of this study was to investigate the inhibitory effect of benzofuran derivatives on 11ß-HSD1 in mesenteric adipose tissue from rodents. 11ß-HSD1 activity was determined by incubation of rat mesenteric adipose tissue microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) with and without benzofuran derivatives (Compounds 1-14). The corticosterone produced was measured by HPLC. More than 40% of 11ß-HSD1 inhibition was observed in Compounds 1, 5, 7 and 8. Moreover, Compounds 7 and 8 inhibited the 11ß-HSD1 activity in adipose microsomes dose- and time-dependently, as well as in 3T3-L1 adipocytes. Compounds 7 and 8 did not inhibit 11ß-HSD type 2 (11ß-HSD2), whereas Compounds 1 and 5 inhibited 11ß-HSD2 by 18.7% and 56.3%, respectively. Further, a kinetic study revealed that Compounds 7 and 8 acted as non-competitive inhibitors of 11ß-HSD1. Ki (nmol/h/mg protein) values of Compounds 7 and 8 were 17.5 and 24.0, respectively, with IC50 (µM) of 10.2 and 25.6, respectively. These data indicate that Compounds 7 and 8 are convincing candidates for seed compounds as specific inhibitors of 11ß-HSD1 and have the potential to be developed as anti-obesity drugs.

Differences between mice strains in response to paroxetine in the forced swimming test: involvement of serotonergic or noradrenergic systems.

We studied the effect of the selective serotonin reuptake inhibitor (SSRI) paroxetine on the immobility time in the forced swimming test using different strains of mice (ICR, ddY, C57BL/6, BALB/c and DBA/2). There was a difference between strains in the response to paroxetine (although it induced anti-immobility effects in all strains of mice used). The mouse strain most sensitive to paroxetine was DBA/2; the ICR strain showed the lowest sensitivity. We previously demonstrated variations in the responses to another SSRI, fluvoxamine, in different strains of mice, which was in agreement with the present findings. In DBA/2 and ICR mice, the anti-immobility effects of paroxetine were significantly antagonized by the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). The noradrenergic α(1)-adrenoceptor antagonist prazosin significantly reduced the anti-immobility effects elicited by a high dose (5mg/kg) of paroxetine in DBA/2 and ICR mice. However, prazosin did not affect the anti-immobility effects of a lower dose of paroxetine (1mg/kg) in DBA/2 mice. This suggests that the anti-immobility effects of a higher dose of paroxetine in mice are associated with serotonergic and noradrenergic neurons. Prazosin did not the affect anti-immobility effects of fluvoxamine. These results suggest that there are differences between mice strains in the antidepressant-like effects of paroxetine (which are similar to those elicited by fluvoxamine). Moreover, involvement of the noradrenergic system was partly related to the anti-immobility effects of paroxetine (which are different to those elicited by fluvoxamine).

Alternative mechanism for anti-obesity effect of dehydroepiandrosterone: possible contribution of 11ß-hydroxysteroid dehydrogenase type 1 inhibition in rodent adipose tissue.

Dehydroepiandrosterone (DHEA) has been suggested to have an anti-obesity effect; however, the mechanism underlying this effect remains unclear. The effect of DHEA on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis. The key to the intracellular activation of glucocorticoids in adipocytes is 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from an inactive 11-keto form (cortisone in humans and 11-dehydrocorticosterone in rodents). In humans and rodents, intracellular glucocorticoid reactivation is exaggerated in obese adipose tissue. Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited about 15.6% of 11ß-HSD1 activity at a concentration of 1 µM within 10min. Inhibition was also observed in a cell-free system composed of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11ß-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11ß-HSD1. Moreover, conversion from DHEA to estrogens was not observed by sensitive semi-micro HPLC equipped with electrochemical detector. These results indicate that the inhibition of 11ß-HSD1 by DHEA depends on neither the transcriptional pathway nor the nonspecific manner. This is the first demonstration that the anti-obesity effect of DHEA is exerted by non-transcriptional inhibition of 11ß-HSD1 in rodent adipocytes.

Involvement of the 5-HT(1A) receptor in the anti-immobility effects of fluvoxamine in the forced swimming test and mouse strain differences in 5-HT(1A) receptor binding.

We previously demonstrated the presence of strain differences in baseline immobility time and sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in five strains of mice (ICR, ddY, C57BL, DBA/2 and BALB/c mice). Furthermore, variations in serotonin (5-HT) transporter binding in the brain were strongly related to strain differences in baseline immobility and sensitivity to fluvoxamine. In the present study, we examined the involvement of the 5-HT(1A) receptor in anti-immobility effects in DBA/2 mice, which show high sensitivity to fluvoxamine. The anti-immobility effects of fluvoxamine in DBA/2 mice were inhibited by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT(1B) receptor antagonist 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide (GR55562), the 5-HT(2) receptor antagonist 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT(3) receptor antagonist ondansetron and the 5-HT(4) receptor antagonist 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not influence the anti-immobility effects of fluvoxamine in DBA/2 mice. These results suggest that fluvoxamine-induced antidepressant-like effects in DBA/2 mice are mediated by the 5-HT(1A) receptor. We analyzed 5-HT(1A) receptor binding in the brains of five strains of mice. Strain differences in 5-HT(1A) receptor binding were observed. 5-HT(1A) receptor binding in brain was not correlated with baseline immobility time in the five strains of mice examined. These results suggest that, although the anti-immobility effects of fluvoxamine in DBA/2 mice are mediated by the 5-HT(1A) receptor, strain differences in 5-HT(1A) receptor binding are not related to variation in immobility time and responses to fluvoxamine.

17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes.

17Beta-estradiol (E(2)) serves as an anti-obesity steroid; however, the mechanism underlying this effect has not been fully clarified. The effect of E(2) on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis and anabolic lipid metabolism. The key to the intracellular activation of glucocorticoid in adipocytes is 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from inactive 11-keto steroids (cortisone in humans and 11-dehydrocorticosterone in rodents). Using differentiated 3T3-L1 adipocytes, we showed that E(2) inhibited 11beta-HSD1 activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed to reverse this inhibition. A significant inhibitory effect of E(2) on 11beta-HSD1 activity was observed within 5-10 min. Furthermore, acetylation or alpha-epimerization of 17-hydroxy group of E(2) attenuated the inhibitory effect on 11beta-HSD1. These results indicate that the inhibition of 11beta-HSD1 by E(2) depends on neither an ER-dependent route, transcriptional pathway nor non-specific fashion. Hexose-6-phosphate dehydrogenase, which provides the cofactor NADPH for full activation of 11beta-HSD1, was unaffected by E(2). A kinetic study revealed that E(2) acted as a non-competitive inhibitor of 11beta-HSD1. The inhibitory effect of E(2) on 11beta-HSD1 was reproduced in adipocytes isolated from rat mesenteric fat depots. This is the first demonstration that E(2) inhibits 11beta-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen.

Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

Comparison of serum cortisol concentrations in preterm infants with or without late-onset circulatory collapse due to adrenal insufficiency of prematurity.

A recent survey found that approximately 4% of very low birth weight infants in Japan were treated with glucocorticoids postnatally for circulatory collapse thought to be caused by late-onset adrenal insufficiency. We identified 11 preterm infants with clinical signs compatible with this diagnosis (hypotension, oliguria, hyponatremia, lung edema, and increased demand for oxygen treatment) and matched them for gestational age with 11 infants without such signs. Blood samples were obtained for cortisol and its precursors from the patient group before the administration of hydrocortisone, and from the control group during the same postnatal week. All samples were analyzed using a gas chromatography-mass spectrometry system. Cortisol concentrations did not differ between the two groups (6.6 +/- 4.5 vs 3.4 +/- 2.7 microg/dL); however, the total concentration of precursors in the pathway to cortisol production was significantly higher in the patient group (72.2 +/- 50.3 vs 25.0 +/- 28.5 microg/dL; p < 0.05). We conclude that the clinical picture of late-onset adrenal insufficiency in preterm infants is not a result of an absolute deficiency of cortisol production, but may be a result of a limited ability to synthesize sufficient cortisol for the degree of clinical stress.

[Controlled release of prednisolone from suppository prepared using powder of pulverized tablet].

Prednisolone suppositories have been used successfully for the treatment of ulcerative colitis in hospital settings. However, the raw material of prednisolone suppository, JP prednisolone powder (JP Powder), was recently removed from the market. Therefore we studied the effects of raw material and suppository base on the release of prednisolone suppository for the purpose of designing a new suppository with similar effects to those of suppository prepared using JP powder (old suppository). New suppositories consisting of the powder of pulverized tablet as raw material and Witepsol H-15 and Witepsol E-75 as suppository base were prepared according to the fusion method. Suppository release test was performed by reciprocating dialysis tube method with tapping (RDT method) and dialysis tubing method (DT method). Both RDT method and DT method were performed using a suppository dissolution apparatus (modified JP disintegration apparatus) and a JP15 paddle apparatus, respectively. The test fluid was 50 mM phosphate buffer solution (pH 7.4) maintained at 37+/-0.5 degrees C. The results of release test by RDT method were similar to those of DT method. Release rate of prednisolone from the new suppository was much faster than that of old suppository. The addition of Witepsol E-75 to new suppository base markedly delayed the release of prednisolone from the new suppository. Release rate of prednisolone from the new suppository, consisting of pulverized tablet and Witepsol H-15 and Witepsol E-75 (76:24), corresponded well with that of the old suppository. It was suggested that this suppository could be used as incoming preparation of suppository prepared using JP powder.

Effects of the serotonin and noradrenaline reuptake inhibitor (SNRI) milnacipran on marble burying behavior in mice.

The effects of milnacipran, a serotonin and noradrenaline reuptake inhibitor (SNRI) on the obsessive compulsive disorder (OCD) model, marble burying behavior, were investigated in mice. Milnacipran above the dosage of 10 mg/kg inhibited marble burying behavior significantly in mice as similar to fluvoxamine. Milnacipran inhibiting marble burying behavior did not affect locomotor activity. These results suggest that milnacipran can inhibit marble burying behavior and that milacipran may be useful for OCD therapy.