The American journal of tropical medicine and hygiene
Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although pe... more Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although periodic ophthalmologic examinations are recommended with weekly suppressive dosing, the occurrence of retinopathy associated with this regimen is unproven. Surveillance of career missionaries was conducted to explore the association between total body burden of chloroquine and the development of retinopathy. Five hundred eighty-eight missionaries, reflecting 6,250 person-years of chloroquine exposure were surveyed; 53 persons reflecting 560 person-years exposure with a median cumulative chloroquine dose in excess of 300 g were examined. Only one case of chloroquine-induced retinopathy was detected. This occurred in a missionary who had inappropriately taken chloroquine daily for at least six years as an anti-inflammatory agent for a connective tissue disorder. We also observed that expatriates often overused chloroquine because of apprehension about malaria and used the drug for unrelated conditions. Our results failed to demonstrate an association between a weekly chloroquine dosing regimen and drug-induced retinopathy.
To determine whether a corticotropin releasing hormone (CRH) type 1-specific receptor antagonist,... more To determine whether a corticotropin releasing hormone (CRH) type 1-specific receptor antagonist, antalarmin, would alter the progression of inflammation in adjuvant induced arthritis (AIA) susceptible LEW/N rats by blocking local CRH mediated inflammatory responses or render AIA resistant F344/N rats more susceptible to AIA by blocking central CRH, thus reducing secretion of endogenous glucocorticoids. F344/N and LEW/N rats were assigned to either drug or vehicle groups and treated with 20 mg/kg antalarmin or vehicle alone BID for 25 days by intraperitoneal injection. Arthritis was induced in both antalarmin and vehicle treated LEW/N and F344/N rats by subcutaneous injections at the base of the tail of incomplete Freund's adjuvant containing 10 mg/ml heat killed Mycobacterium tuberculosis. Control F344/N and LEW/N rats were maintained on either antalarmin or vehicle. Chronic blockade of CRH-R1 with systemic antalarmin significantly ameliorated AIA in LEW/N rats, reducing the se...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evalua... more A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load. Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture. The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral ther...
Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is c... more Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-(18F)fluoro-3-(2(S)azetidinylmethoxy)pyridine (2- (18F)FA). We acquired scans from six healthy
Prior studies have reported men with coronary artery disease (CAD) to have elevated plasma levels... more Prior studies have reported men with coronary artery disease (CAD) to have elevated plasma levels of estrogens and reduced concentrations of dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS). We investigated whether gonadal steroids or DHEAS are risk factors for CAD in men, using a prospective design, in a well characterized population studied at regular intervals. We studied 46 men (Cardiac group) who developed CAD and 124 men (Control group) who remained free of CAD (mean follow-up, 9.5 years). We measured testosterone (T), estradiol (E2), and DHEAS, as well as plasma binding of T and E2, in samples stored before the onset of CAD (Cardiac group) or at matched times (Control group). Body mass index, blood pressure, and total serum cholesterol were measured at each visit. Both systolic blood pressure (SBP; P less than 0.001) and cholesterol (P less than 0.001) were increased in the Cardiac group, but no significant differences were found in total or free T or E2, the ratio of E2...
The rewarding effects of nicotine are associated with activation of nicotine receptors. However, ... more The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions we...
Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficac... more Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morp...
[(18)F]FCWAY and [(18)F]FPWAY, analogues of the high affinity 5-HT(1A) receptor (5-HT(1A)R) antag... more [(18)F]FCWAY and [(18)F]FPWAY, analogues of the high affinity 5-HT(1A) receptor (5-HT(1A)R) antagonist WAY100635, were evaluated in rodents as potential radiopharmaceuticals for determining 5-HT(1A)R density and changes in receptor occupancy due to changes in endogenous serotonin (5-HT) levels. The in vivo hippocampus specific binding ratio [(hippocampus(uptake)/cerebellum(uptake))-1] of [(18)F]FPWAY was decreased to 32% of the ratio of [(18)F]FCWAY, indicating that [(18)F]FPWAY has lower affinity than [(18)F]FCWAY. The 5-HT(1A)R selectivity of [(18)F]FPWAY was confirmed using ex vivo autoradiography studies with 5-HT(1A)R knockout, heterozygous, and wildtype mice.Pre- or post-treatment of awake rodents in tissue dissection studies with paroxetine had no effect on hippocampal binding of [(18)F]FCWAY or [(18)F]FPWAY compared to controls, indicating neither tracer was sensitive to changes in endogenous 5-HT. In mouse ex vivo autoradiography studies in which awake mice were treated with fenfluramine following the [(18)F]FPWAY, a significant decrease was not observed in the hippocampus specific binding ratios. In rat dissection studies with fenfluramine administered following [(18)F]FPWAY or [(18)F]FBWAY ([(18)F]-MPPF) in awake or urethane-anesthetized rats, no significant differences in the specific binding ratios of the hippocampus were observed compared to their respective controls. [(18)F]FPWAY and [(18)F]FBWAY uptakes in all brain regions were increased variably in the anesthetized group (with the greatest increase in the hippocampus) vs. the awake group, but were decreased in the fenfluramine-treated anesthetized group vs. the anesthetized group. These data are best explained by changes in blood flow caused by urethane and fenfluramine, which varies from region to region in the brain.
The American journal of tropical medicine and hygiene
Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although pe... more Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although periodic ophthalmologic examinations are recommended with weekly suppressive dosing, the occurrence of retinopathy associated with this regimen is unproven. Surveillance of career missionaries was conducted to explore the association between total body burden of chloroquine and the development of retinopathy. Five hundred eighty-eight missionaries, reflecting 6,250 person-years of chloroquine exposure were surveyed; 53 persons reflecting 560 person-years exposure with a median cumulative chloroquine dose in excess of 300 g were examined. Only one case of chloroquine-induced retinopathy was detected. This occurred in a missionary who had inappropriately taken chloroquine daily for at least six years as an anti-inflammatory agent for a connective tissue disorder. We also observed that expatriates often overused chloroquine because of apprehension about malaria and used the drug for unrelated conditions. Our results failed to demonstrate an association between a weekly chloroquine dosing regimen and drug-induced retinopathy.
To determine whether a corticotropin releasing hormone (CRH) type 1-specific receptor antagonist,... more To determine whether a corticotropin releasing hormone (CRH) type 1-specific receptor antagonist, antalarmin, would alter the progression of inflammation in adjuvant induced arthritis (AIA) susceptible LEW/N rats by blocking local CRH mediated inflammatory responses or render AIA resistant F344/N rats more susceptible to AIA by blocking central CRH, thus reducing secretion of endogenous glucocorticoids. F344/N and LEW/N rats were assigned to either drug or vehicle groups and treated with 20 mg/kg antalarmin or vehicle alone BID for 25 days by intraperitoneal injection. Arthritis was induced in both antalarmin and vehicle treated LEW/N and F344/N rats by subcutaneous injections at the base of the tail of incomplete Freund's adjuvant containing 10 mg/ml heat killed Mycobacterium tuberculosis. Control F344/N and LEW/N rats were maintained on either antalarmin or vehicle. Chronic blockade of CRH-R1 with systemic antalarmin significantly ameliorated AIA in LEW/N rats, reducing the se...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evalua... more A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load. Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture. The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral ther...
Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is c... more Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-(18F)fluoro-3-(2(S)azetidinylmethoxy)pyridine (2- (18F)FA). We acquired scans from six healthy
Prior studies have reported men with coronary artery disease (CAD) to have elevated plasma levels... more Prior studies have reported men with coronary artery disease (CAD) to have elevated plasma levels of estrogens and reduced concentrations of dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS). We investigated whether gonadal steroids or DHEAS are risk factors for CAD in men, using a prospective design, in a well characterized population studied at regular intervals. We studied 46 men (Cardiac group) who developed CAD and 124 men (Control group) who remained free of CAD (mean follow-up, 9.5 years). We measured testosterone (T), estradiol (E2), and DHEAS, as well as plasma binding of T and E2, in samples stored before the onset of CAD (Cardiac group) or at matched times (Control group). Body mass index, blood pressure, and total serum cholesterol were measured at each visit. Both systolic blood pressure (SBP; P less than 0.001) and cholesterol (P less than 0.001) were increased in the Cardiac group, but no significant differences were found in total or free T or E2, the ratio of E2...
The rewarding effects of nicotine are associated with activation of nicotine receptors. However, ... more The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions we...
Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficac... more Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morp...
[(18)F]FCWAY and [(18)F]FPWAY, analogues of the high affinity 5-HT(1A) receptor (5-HT(1A)R) antag... more [(18)F]FCWAY and [(18)F]FPWAY, analogues of the high affinity 5-HT(1A) receptor (5-HT(1A)R) antagonist WAY100635, were evaluated in rodents as potential radiopharmaceuticals for determining 5-HT(1A)R density and changes in receptor occupancy due to changes in endogenous serotonin (5-HT) levels. The in vivo hippocampus specific binding ratio [(hippocampus(uptake)/cerebellum(uptake))-1] of [(18)F]FPWAY was decreased to 32% of the ratio of [(18)F]FCWAY, indicating that [(18)F]FPWAY has lower affinity than [(18)F]FCWAY. The 5-HT(1A)R selectivity of [(18)F]FPWAY was confirmed using ex vivo autoradiography studies with 5-HT(1A)R knockout, heterozygous, and wildtype mice.Pre- or post-treatment of awake rodents in tissue dissection studies with paroxetine had no effect on hippocampal binding of [(18)F]FCWAY or [(18)F]FPWAY compared to controls, indicating neither tracer was sensitive to changes in endogenous 5-HT. In mouse ex vivo autoradiography studies in which awake mice were treated with fenfluramine following the [(18)F]FPWAY, a significant decrease was not observed in the hippocampus specific binding ratios. In rat dissection studies with fenfluramine administered following [(18)F]FPWAY or [(18)F]FBWAY ([(18)F]-MPPF) in awake or urethane-anesthetized rats, no significant differences in the specific binding ratios of the hippocampus were observed compared to their respective controls. [(18)F]FPWAY and [(18)F]FBWAY uptakes in all brain regions were increased variably in the anesthetized group (with the greatest increase in the hippocampus) vs. the awake group, but were decreased in the fenfluramine-treated anesthetized group vs. the anesthetized group. These data are best explained by changes in blood flow caused by urethane and fenfluramine, which varies from region to region in the brain.
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Papers by Carlo Contoreggi