A pilot dose-finding study of Terazosin in humans.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects.

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism.

The brain-specific isoform of renin (Ren-b) has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-b mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-b mice are unknown.

Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients.

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity.

Methods And Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow.

Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy.

Pharmacological ascorbate (AscH(-)) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells compared with normal cells. Positron emission tomography (PET) with the thymidine analog 3'-deoxy-3'-((18)F) fluorothymidine (FLT) enables noninvasive imaging and quantification of the proliferation fraction of tumors. We hypothesized that the rate of tumor proliferation determined by FLT-PET imaging, would be inversely proportional to tumor susceptibility to pharmacological AscH(-)-based treatments.

Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury.

This study aimed to examine global and regional cerebral blood flow and amyloid burden in combat veterans with and without traumatic brain injury (TBI). Cerebral blood flow (in milliliters per minute per 100 mL) was measured by quantitative [(15)O]water, and amyloid burden was measured by [(11)C]PIB imaging. Mean global cerebral blood flow was significantly lower in veterans with TBI compared with non-TBI veterans.

Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus.

Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4R(LHA) signaling regulates glucose tolerance and sympathetic nerve activity.

Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study.

Purpose: The term "chemobrain" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment. As breast cancer survivors now commonly reach late life, it is not known whether previous exposure to chemotherapy may affect long-term risk for cognitive impairment. To help address this concern, this study tested whether successfully surviving chemotherapy earlier in life was associated with later differences in brain metabolic function as an older adult compared to controls.

Repeatability of gallium-68 DOTATOC positron emission tomographic imaging in neuroendocrine tumors.

Objective: To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors.

Methods: Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured.

The biology of linguistic expression impacts neural correlates for spatial language.

Biological differences between signed and spoken languages may be most evident in the expression of spatial information. PET was used to investigate the neural substrates supporting the production of spatial language in American Sign Language as expressed by classifier constructions, in which handshape indicates object type and the location/motion of the hand iconically depicts the location/motion of a referent object. Deaf native signers performed a picture description task in which they overtly named objects or produced classifier constructions that varied in location, motion, or object type.

Eyeblink conditioning in healthy adults: a positron emission tomography study.

Eyeblink conditioning is a paradigm commonly used to investigate the neural mechanisms underlying motor learning. It involves the paired presentation of a tone-conditioning stimulus which precedes and co-terminates with an airpuff unconditioned stimulus. Following repeated paired presentations a conditioned eyeblink develops which precedes the airpuff.

Sign language and pantomime production differentially engage frontal and parietal cortices.

We investigated the functional organization of neural systems supporting language production when the primary language articulators are also used for meaningful, but non-linguistic, expression such as pantomime. Fourteen hearing non-signers and 10 deaf native users of American Sign Language (ASL) participated in an H(2) (15)O-PET study in which they generated action pantomimes or ASL verbs in response to pictures of tools and manipulable objects. For pantomime generation, participants were instructed to "show how you would use the object.

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy.

Background And Purpose: The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [(18)F]FLT PET imaging.

Materials And Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using [(18)F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4>SUV3 ≥ 3; and 3 > SUV2 ≥ 2.

Effect of insulin and dexamethasone on fetal assimilation of maternal glucose.

The growing fetus depends upon transfer of glucose from maternal blood to fetal tissues. Insulin and glucocorticoid impact maternal glucose metabolism, but the effects of these hormones on fetal glucose assimilation in vivo are understudied. We thus used positron emission tomography imaging to determine the disposition of [(18)F]fluorodeoxyglucose (FDG) in rats on gestational d 20, quantifying the kinetic competition of maternal tissues and fetus for glucose.

Localized fetomaternal hyperglycemia: spatial and kinetic definition by positron emission tomography.

Background: Complex but common maternal diseases such as diabetes and obesity contribute to adverse fetal outcomes. Understanding of the mechanisms involved is hampered by difficulty in isolating individual elements of complex maternal states in vivo. We approached this problem in the context of maternal diabetes and sought an approach to expose the developing fetus in vivo to isolated hyperglycemia in the pregnant rat.

Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer.

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer.

Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET.

Neural bases of dysphoria in early Huntington's disease.

Psychiatric disorders, including disorders of emotion control, are common in Huntington's disease. The neurobiological mechanism of the increased rate of disorders of emotion control are not known. Emotion perception deficits have been reported in Huntington's disease, but studies of emotional experience have been limited.

The neural correlates of implicit sequence learning in schizophrenia.

Twenty-seven schizophrenia spectrum patients and 25 healthy controls performed a probabilistic version of the serial reaction time task (SRT) that included sequence trials embedded within random trials. Patients showed diminished, yet measurable, sequence learning. Postexperimental analyses revealed that a group of patients performed above chance when generating short spans of the sequence.

The neural correlates of spatial language in English and American Sign Language: a PET study with hearing bilinguals.

Rather than specifying spatial relations with a closed-class set of prepositions, American Sign Language (ASL) encodes spatial relations using space itself via classifier constructions. In these constructions, handshape morphemes specify object type, and the position of the hands in signing space schematically represents the spatial relation between objects. A [15O]water PET study was conducted to investigate the neural regions engaged during the production of English prepositions and ASL locative classifier constructions in hearing subjects with deaf parents (ASL-English bilinguals).

Effect of acute marijuana on cardiovascular function and central nervous system pharmacokinetics of [(15)O]water: effect in occasional and chronic users.

The objective of this study was to evaluate the effect of the acute administration of marijuana (MJ) on cardiovascular (CV) function and CNS pharmacokinetics (PK) of [(15)O]water in occasional (O) versus chronic (C) MJ users. Each subject received four injections of [(15)O]water (one prior and three postsmoking) on two occasions in which they received active or placebo MJ. For each injection, measures of CV function and CNS PK [(15)O]water were made.

Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter.

Unlabelled: In this study we investigated the feasibility of using radionuclide accumulation mediated by the human sodium iodide symporter (hNIS) gene in conjunction with various imaging modalities as a reporter system to noninvasively monitor the expression of transgenes delivered for gene therapy.

Methods: NIS-expressing adenovirus (Ad-hNIS) was delivered in vitro to MB-435 breast carcinoma cells. NIS-mediated accumulation of (125)I(-), (99m)TcO(4)(-), and (76)Br(-) by the cells was visualized using autoradiography, gamma-camera scintigraphy, and PET imaging, respectively.

[15O]water pharmacokinetics: influence of age and gender in normal subjects.

Purpose: To compile a normal database for the characterization of global [15O]water pharmacokinetic behavior.

Procedures: The influences of age, gender, and body habitus on the pharmacokinetics of [15O]water were investigated in a series of normal subjects, N = 100 (50 males, 50 females, age = 19-79) who were participants in cognitive activation studies. Arterial blood was analyzed by autosampler and parametric images were constructed using a 40-second summed image and the autoradiographic model.

Contamination levels in blood samples drawn from the injection intravenous line.

Purpose: Securing two intravenous lines, one for injection and one for blood sampling, can be nearly impossible in compromised patients, therefore, a need exists to quantify the potential error when simplified techniques are employed.

Method: Two venous catheters were placed. 2-deoxy-2-[18F]fluoro-glucose (FDG) was infused through one of the catheters.

Assessment of Blood Flow in Solid Tumors Using PET.

OBJECTIVE: To develop a technique for the evaluation of tumor perfusion prior to and during chemo- and radiation therapy.METHODS: Using the [(15)O]water autoradiographic technique and positron emission tomography (PET), perfusion in solid cervical tumors was investigated in a series of women prior to and during radiation therapy for cervical cancer. A 60-second summed image was used with the arterial blood curve to create a parametric image.

Ginkgo biloba extract: review of CNS effects.

The marketing of Ginkgo biloba extract (GBE) products is directed to the healthy, not diseased, population primarily for the promotion and maintenance of optimal brain function, not the treatment or prevention of any specific pathological state. However, recommendations are available for the use of GBE for a myriad of diseases that generally fall into one of three categories--cerebrovascular, peripheral vascular, or mitigation of tissue damage. The evidence for the pharmacological actions of GBE stem from one of three types of investigations--clinical studies in humans, pharmacological trials in animals, and in vitro studies.