Faculty Bibliography

Background: Quinine is an alkaloid naturally occurring in the crust of some trees of genus Rubiaceae, traditionally used for the treatment of malaria, seizures, and various,infections. In this work we present results of samples tested in Spain, both of the concentration found and labelling, as well as related to the potential implications of quinine on public health,. Methods: The content of quinine was analyzed in 11 samples of tonic waters in the Spanish market by liquid chromatography coupled through laser induced fluorescence detection. Results: The method used is characterized by its accuracy, speed and sensitivity. Quinine concentration in beverages is not homogeneous. The labelling does not indicate the quinine content. Conclusions: More specific regulation is needed as well as more information to consumers, especially for certain risk groups.

(S)-5-[(123)I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[(123)I]IA), a novel potent radioligand for high-affinity alpha4beta2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5-[(123)I]IA in an open nonblind trial and (2) to estimate the density and the distribution of alpha(4)beta(2)* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of approximately 0.001 microg/kg ( approximately 10 mCi) 5-[(123)I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[(123)I]IA to 12 healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma-nicotine level was significantly associated with low 5-[(123)I]IA binding in: (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann-Whitney U-tests; (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann-Whitney U-test; and (3) the thalamus utilizing the Sign test. We conclude that 5-[(123)I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity alpha4/beta2 nAChRs in the living human brain.

The widely used Logan plot in radioligand receptor dynamic PET studies produces marked noise-induced negative biases in the estimates of total distribution volume (DV(T)) and binding potential (BP). To avoid the inconsistencies in the estimates from the Logan plot, a new graphical analysis method was proposed and characterized in this study. The new plot with plasma input and with reference tissue input was first derived to estimate DV(T) and BP. A condition was provided to ensure that the estimate from the new plot equals DV(T) or BP. It was demonstrated theoretically that 1) the statistical expectations of the estimates from the new plot with given input are independent of the noise of the target tissue concentration measured by PET; and 2) the estimates from the time activity curves of regions of interest are identical to those from the parametric images for the new plot. The theoretical results of the new plot were also confirmed by computer simulations and fifty-five human [(11)C]raclopride dynamic PET studies. By contrast, the marked noise-induced underestimation in the DV(T) and BP images and noise-induced negative bias in the estimates from the Logan plot were demonstrated by the same data sets used for the new plot. The computational time for generating DV(T) or BP images in the human studies was reduced by 80% on average by the new plot in contrast to the Logan plot. In conclusion, the new plot is a consistent and computationally efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies.

Brain imaging represents a potent tool to characterize biomarkers, biological traits that are pathognomonic for specific neurological and neuropsychiatric disorders. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are imaging techniques used to identify alterations in the density and distribution of neurotransmitters, neuroreceptors, and transporters in specific regions of the brains of people with these disorders. Brain imaging research currently facilitates the elucidation of dysfunction of dopamine, serotonin, acetylcholine, and other substances in people with Alzheimer's and Parkinson's diseases, schizophrenia, alcoholism and other substance abuse disorders, attention deficit/hyperactivity disorder, and the syndromes of restless legs, Lesch-Nyhan, Rett, and Tourette. Thus, brain imaging research offers great potential for the diagnosis, treatment, prevention, and cure of neurological and neuropsychiatric disorders. Brain imaging research also facilitates new drug development and helps establish therapeutic doses of novel drugs. In particular, studies of specific receptors, such as the dopamine D2 receptor, before and after the administration of doses of drugs that occupy these D2 receptors, provide the means to determine receptor occupancy. For example, an optimal dose of D2 antagonist antipsychotics produces occupancy of 65% to 80% of D2 receptors, while a greater dose carries a risk of extrapyramidal side effects.

To investigate the possible association of obstetric complications and autistic disorder, we performed a review of case-control studies of any obstetric complication in autistic disorder. If the odds ratio = {(Number of cases with autistic disorder with any obstetric complication)/(Number of cases with autistic disorder without any obstetric complication)}/{(Number of controls without autistic disorder with any obstetric complication)/(Number of controls without autistic disorder without any obstetric complication)} <1, then there are more complications in controls; =1, then complications are equal in cases and controls; and >1, then there are more complications in cases. Most publications do not provide the raw data to calculate the odds ratio. Many calculated odds ratios support the hypothesis that cases with autism have more obstetric complications. Further investigation is warranted to clarify the relationships between obstetric complications and autism and related conditions in the general population worldwide.