Etiology, diagnostic modalities, and short-term outcomes of hemoptysis-a retrospective cross-sectional study from a tertiary care center in Qatar.

Background: Hemoptysis is a concerning symptom characterized by the expectoration of blood from the respiratory tract, which can range from mild to life-threatening. It can be caused by various underlying conditions. Accurate diagnosis is critical for effective management.

A Novel Understanding of Phocidae Hearing Adaptations Through a Study of Northern Elephant Seal (Mirounga angustirostris) Ear Anatomy and Histology.

The most conspicuous aural adaptation in northern elephant seals (NES) is complete absence of an auricle and a tortuous collapsed external acoustic meatus. The NES epitympanic recess contains massive ossicles immersed in the middle ear cavernous sinuses. Engorgement of the cavernous sinuses would make ossicles fully buoyant during deep diving.

Histological Characteristics of the Tracheobronchial Tree of the Least Shrew (Cryptotis Parva).

The least shrew (Cryptotis parva) is a small vomit-competent insectivorous species which has recently been introduced as an emesis animal model in the laboratory. In this study, the respiratory system of the least shrew was examined and compared with the well-established larger species routinely used in the laboratory. Five least shrews (4-5 g body weight, 45-60 days old) were used.

Ultrastructure of Developing Feline Nonciliated Bronchiolar Epithelial Cells.

The ultrastructure of the developing bronchiolar cell was studied in six age groups: prenatal (60 d post-conception); postnatal (1-, 7-, 14- and 21-day-old); and adult. Following intratracheal fixation, the lung tissue was processed for scanning and transmission electron microscopy. The lining of terminal bronchioles consists of cuboidal to columnar nonciliated bronchiolar cells (NBCs) and ciliated with or without microvilli.

Histomorphology and immunohistochemistry of the lower esophageal sphincter of the least shrew (Cryptotis parva).

The biochemical and histopathological changes in the lower esophageal sphincter (LES) in the pathogenesis of gastroesophageal reflux disease have gained interest. The least shrew is able to vomit in response to emetogens and provides a good model to study the histology of this phenomenon relative to the published reports in the commonly used but vomit-incompetent laboratory species. The LES is located at the junction of the esophagus and stomach.

SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain.

Introduction: Serotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2beta-carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [(123)I]p ZIENT, in nonhuman primate brain.

Methods: Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.

Synthesis, radiolabeling and baboon SPECT imaging of 2beta-carbomethoxy-3beta-(3'-[(123)I]iodophenyl)tropane ([(123)I]YP256) as a serotonin transporter radiotracer.

To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2beta-carbomethoxy-3beta-(3'-[(123)I]iodophenyl) tropane (YP256, 6). The radiolabeling was performed by iododestannylation using sodium [(123)I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

Synthesis and monoamine transporter affinity of 2beta-carbomethoxy-3beta-(4'-p-substituted phenyl)-piperidine analogs of cocaine.

A series of novel piperidine based analogs of cocaine was synthesized and evaluated in vitro against the three monoamine transporters to develop new potential selective SERT radiotracers. Modification of the phenyl substitution with five-membered heterocyclic groups resulted in a wide affinity and selectivity scale. Radiolabeling and mouse in vivo study was performed on the piperidine analog of ZIENT, which crossed the blood-brain barrier but failed to selectively accumulate in the regions of the brain rich in SERT.

Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma.

The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.

Radiosynthesis of [18F] N-(3-Fluoropropyl)-2-beta-Carbomethoxy-3-beta-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET.

A synthetic procedure for the preparation of [18F]FPCBT, an imaging agent for the dopamine transporter (DAT), has been developed. The radiosynthesis was carried out in a two step procedure. Even though the yield was low, we were able to prepare 20 to 30 mCi of the product, which was enough for two or three studies.

Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor ligand [123I]5-I-A-85380.

Although in vitro theory indicates that ligand binding is sensitive to competition with neurotransmitters, only some imaging ligands have shown such competition in vivo. The purpose of this study was to determine whether increases in acetylcholine (ACh) levels induced by an acetylcholinesterase inhibitor, physostigmine, inhibit in vivo binding of [(123)I]5-iodo-3-(2(S)-2-azetidinyl-methoxy) pyridine (5-I-A-85380), a single photon emission computed tomography ligand for the high-affinity type nicotinic ACh receptor (nAChR). Baboons were used for seven studies with a bolus plus constant infusion equilibrium paradigm.

Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h.

Measurement of plasma metabolites of (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates.

The iodinated analog (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine of A-85380 is a new potential SPECT tracer specific for the alpha4beta2 subtype nicotinic acetylcholine receptors, which play an important role in neurodegenerative diseases and in tobacco dependence. To evaluate the possibility of using this tracer for the in vivo quantification of these receptors, an accurate measurement of the plasma concentration of the parent compound is necessary. In human or nonhuman primate whole blood as well as in plasma, the parent compound is only stable for approximately 5 min, after which it decomposes.

SPECT imaging with the D(4) receptor antagonist L-750,667 in nonhuman primate brain.

The suitability of an (123)I-labeled form of the putative D(4) receptor ligand L750,667 as a radiotracer for single photon emission computed tomography imaging was assessed in nonhuman primates. [(123)I]L750,667, labeled by iododestannylation, was administered to baboons in bolus and bolus plus constant infusion paradigms and imaged for 6 h. Total [(123)I]L750,667 brain uptake peaked (2.

Measurement of alpha4beta2 nicotinic acetylcholine receptors with [123I]5-I-A-85380 SPECT.

Unlabelled: Nicotinic acetylcholine receptors (nAChRs) play an important role in tobacco dependence and a potential therapeutic role in neuropsychiatric disorders such as Alzheimer's disease. [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) is a new SPECT tracer that labels alpha4beta2 nAChRs. The purpose of this study was to assess the usefulness of this tracer to measure regional nAChR binding in baboon brain using both a bolus/kinetic paradigm and also a bolus plus constant infusion/equilibrium paradigm.

[123I]IPCIT and [123I]beta-CIT as SPECT tracers for the dopamine transporter: a comparative analysis in nonhuman primates.

[123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]-CIT) and its isopropylester analog [123I]PCIT, both of which are phenyltropane derivatives of cocaine with high affinity for the dopamine (DA) transporter, were compared using single photon emission computed tomography in nonhuman primates. Although IPCIT is significantly more selective for the DA transporter than beta-CIT, striatal distribution volumes of specifically bound tracer were similar for both tracers. Compartmental modeling results were compared with a simple peak equilibrium method used previously by this group.

Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine.

Previously we have shown that twelve weeks of repeated low-dose d-amphetamine (AMPH) exposure in rhesus monkeys induces a long-lasting enhancement of behavioral responses to acute low-dose challenge. The present study was designed to investigate the behavioral and neurochemical consequences of a six-week regimen of low-dose AMPH exposure (0.1-1.

Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent.

This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography. In analogy to its analog ketanserin, we postulated 4-(4-fluorobenzoyl)piperidine (FBP) and altanserinol for the previously observed two polar radiometabolites, corresponding to dealkylation at the piperidine nitrogen and reduction at the ketone, respectively. To test this hypothesis and characterize the in vivo and in vitro behavior of the radiometabolites, we synthesized nonradioactive authentic compounds altanserinol, 1-(4-fluorophenyl)-1-(piperidin-4-yl)methanol (FBPOH), and isolated nonradioactive FBP metabolite from monkey plasma.

Radiosynthesis and PET imaging of [N-methyl-11C]LY257327 as a tracer for 5-HT transporters.

No-carrier-added [N-methyl-11C]LY257327 was synthesized by methylation of the free base of the desmethyl precursor LY214281 with [11C]methyl iodide in anhydrous acetonitrile. Synthesis time was 52 +/- 3 min, radiochemical yield (based on [11C]methyl iodide) was 35 +/- 8%, radiochemical purity was 99 +/- 1%, and specific activity at EOB was 3900 +/- 1300 mCi/mumol. Two in vivo studies in baboon were carried out before and after pretreatment with the selective serotonin reuptake inhibitor citalopram.

Preclinical evaluation of [123I]R93274 as a SPECT radiotracer for imaging 5-HT2A receptors.

Studies in rodents have suggested that the radioiodinated 5-HT2A receptor antagonist [123I]R93274 (123-iodine-N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-ami no- 5-iodo-2-methoxybenzamide) (Kd = 0.1 nM) might be a promising single photon emission computerized tomography (SPECT) radiotracer to image 5-HT2A receptors in the living human brain. In this study, we characterized the brain uptake of [123I]R93274 in baboons.

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates.

The competition between endogenous transmitters and radiolabeled ligands for in vivo binding to neuroreceptors might provide a method to measure endogenous transmitter release in the living human brain with noninvasive techniques such as positron emission tomography (PET) or single photon emission computerized tomography (SPECT). In this study, we validated the measure of amphetamine-induced dopamine release with SPECT in nonhuman primates. Microdialysis experiments were conducted to establish the dose-response curve of amphetamine-induced dopamine release and to document how pretreatment with the dopamine depleter alpha-methyl-para-tyrosine (alpha MPT) affects this response.

Restoration of dopamine transporter density in the striatum of fetal ventral mesencephalon-grafted, but not sham-grafted, MPTP-treated parkinsonian monkeys.

Transplantation of fetal dopamine neurons to the adult striatum potentially offers a means to reverse the striatal dopamine deficiency that characterizes Parkinson's disease. Many investigations in rodents have supported the hope that neural grafting may be a useful treatment for parkinsonism. However, clinical studies have generally produced more modest improvements in motor abnormalities than observed in lower species.

Characterization of the dopamine transporter in nonhuman primate brain: homogenate binding, whole body imaging, and ex vivo autoradiography using [125I] and [123I]IPCIT.

IPCIT [2 beta-carboisopropoxy-3 beta-(4-iodophenyl)tropane; also designated RTI-121] is the isopropyl ester of beta-CIT [2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane]. Although beta-CIT binds to dopamine (DA), serotonin (5-HT) and norepinephrine (NE) transporters, IPCIT has been reported to be selective for the DA transporter. IPCIT was labeled with 125I and its receptor binding to membranes prepared from baboon striatum was compared with that of [125I] beta-CIT.

Regional brain uptake and pharmacokinetics of [123I]N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane esters in baboons.

Four N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane ester (beta-CIT-FE), N-fluoropropyl, methyl ester (beta-CIT-FP), N-fluoroethyl, isopropyl ester (IP-beta-CIT-FE), and N-fluoropropyl, isopropyl ester (IP-beta-CIT-FP)] were labeled with 125I and evaluated in baboons by dynamic SPECT regional brain imaging, measurement of pharmacokinetics in arterial plasma, and whole body imaging. The labeled tracers were prepared by iododestannylation of the corresponding 4-(trimethylstannyl)phenyl compounds in radiochemical yield 63-96% and radiochemical purity > 96%. Regional SPECT brain imaging was carried out over a period of 5 h with a Strichman 810X Brain Imager to assess regional uptake in the striatum and midbrain compared to reference regions in the occipital cortex and cerebellum; arterial blood samples were taken for analysis of metabolites by solvent extraction and HPLC.

Comparison of [123I]beta-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates.

Single-photon emission tomographic (SPET) imaging with the radiotracer [123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity, beta-CIT also binds with high affinity to serotonin (5-HT) transporters. 2 beta-Carboisopropoxy-3 beta-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter.