Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D_2/3 receptors (D_2/3R) in humans in vivo. Our group has developed [¹¹C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D₃R. Thus, the use of [¹¹C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D_2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D₃R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [¹¹C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [¹¹C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D₂R-rich regions (caudate and putamen), mixed D_2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D₃R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [¹¹C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D₂R and D₃R in neuropsychiatric populations.     

Remodeling of the cytoskeletal lattice in denervated skeletal muscle

The effect of denervation-induced atrophy on the cytoskeletal lattice in rat fast- and slow-twitch skeletal muscle has been investigated. Immunochemical analyses and immunofluorescence microscopy experiments employing monospecific antibodies to dystrophin, desmin, and α-tubulin were carried out on intact and denervated muscles. The relative cellular content of dystrophin and desmin were reduced in the soleus muscle (slow-twitch), while significant increases were shown in the gastrocnemius muscle (fast-twitch). In both muscles, α-tubulin levels increased up to 12-fold as a function of time compared to control values. Immunofluorescence microscopy revealed a distinct rearrangement of the microtubule network toward a predominantly longitudinal alignment, which was accompanied by an increase in the density of the fluorescence. It is concluded that the relative increase of the three structural proteins in the fast-twitch gastrocnemius muscle may be related to the apparent resistance of this muscle type to denervation-induced atrophy. The increased α-tubulin content in denervated slow- and fast-twitch muscles could be indicative of an adaptive mechanism designed to maintain the integrity of the muscle fiber in view of eventual regenerative activities. © 1996 John Wiley & Sons, Inc.     

以肺部超声为应用的多学科诊疗体系在高原性肺水肿诊疗中的价值

目的　探索以肺部超声为应用的多学科诊疗体系在高原性肺水肿诊疗中的价值。方法　选取 2018—2022年在甘孜州稻城县人民医院急诊科收治的 200例疑似高原性肺水肿患者为研究对象,将其中确诊的 115例患 者按照平衡序贯法随机分为试验组（采用以肺部超声为应用的多学科诊疗体系,n=56）和对照组（采用常规诊疗方式, n=59）,比较两组的诊疗效果。结果　在早期诊断高原性肺水肿中,肺部超声的灵敏度、正确指数及阴性预测值均高于X 线检查结果（P<0.05）,而与CT检查结果比较差异无统计学意义（P>0.05）。试验组的诊疗时效性、抗生素使用率、心衰 发生率、无创呼吸机上机率、康复期恢复等方面优于对照组（P<0.05）。结论　以肺部超声为应用的多学科诊疗体系在 高原性肺水肿早期诊断中具有较高的灵敏度、正确指数及阴性预测值,可促进患者愈后及康复。     

Motives for parenthood and response to failed in vitro fertilization: Implications for counseling

The purpose of this investigation was to identify in vitro fertilization (IVF) candidates' motives for parenthood and hence for seeking treatment. The relationship among identified motives, pretreatment emotional adjustment, and reaction to treatment failure was then examined. Women as a group placed greatest emphasis on fulfilling gender-role requirements, and those strongly endorsing such motives showed the poorest adjustment before IVF and the most negative reaction to first-cycle failure. In contrast, men in general were more likely to stress a desire for marital completion, although this motive was not predictive of emotional status before or after IVF. However, men experiencing social pressures to have children were at greater risk when treatment failed. The results indicate that greater consideration of cognitive factors may enhance understanding of emotional reactions to IVF failure and provide important insights for therapeutic intervention.     

Bupropion occupancy of the dopamine transporter is low during clinical treatment

RATIONALE: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design. RESULTS: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.