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British Medical Journal Nov 1963
Topics: Appetite Depressants; Chlorphentermine; Pharmacology; Substance-Related Disorders; Toxicology
PubMed: 14056912
DOI: 10.1136/bmj.2.5367.1269 -
Journal of Nuclear Medicine : Official... Apr 1986N-[11C-methyl]chlorphentermine ([11C]NMCP) and N,N-[11C-dimethyl]chlorphentermine ([11C]NDMCP) were prepared from chlorphentermine and 11CH3I in DMF and evaluated in...
N-[11C-methyl]chlorphentermine ([11C]NMCP) and N,N-[11C-dimethyl]chlorphentermine ([11C]NDMCP) were prepared from chlorphentermine and 11CH3I in DMF and evaluated in rats as brain blood-flow agents for positron emission tomography (PET). Tissue distribution of [11C]NMCP showed that brain uptake was 2.70 +/- 0.40% of injected dose per organ at 5 min with no change in radioactivity concentration up to 30 min after i.v. injection. Approximately 80% of the initial brain uptake remained at 60 min. On the other hand, initial brain uptake of [11C] NDMCP (3.66 +/- 0.31 and 3.63 +/- 0.88% injected dose per organ at 5 and 15 min, respectively) was greater than that of [11C]NMCP. The brain activity however, rapidly decreased to 2.38 +/- 0.17 and 1.82 +/- 0.32% at 30 and 60 min, respectively. Because of its longer retention in the brain compared with [11C]NDMCP, [11C]NMCP would be a potential brain blood-flow agent for quantitative PET studies.
Topics: Animals; Brain; Carbon Radioisotopes; Cerebrovascular Circulation; Chlorphentermine; Drug Evaluation; Phentermine; Rats; Tissue Distribution; Tomography, Emission-Computed
PubMed: 3486957
DOI: No ID Found -
Malaria Journal Dec 2022Routine continuous distribution (CD) of insecticide-treated nets (ITNs) has been an important part of an overall ITN strategy to complement mass campaigns since the... (Review)
Review
BACKGROUND
Routine continuous distribution (CD) of insecticide-treated nets (ITNs) has been an important part of an overall ITN strategy to complement mass campaigns since the early 2000s. The backbone of CD implementation for many sub-Saharan African countries is distribution through antenatal care (ANC) and Expanded Programme for Immunizations (EPI) channels. Performance of these channels is often not monitored closely at the national level, nor is it reviewed globally, unlike the oversight provided to mass campaigns. The question as to why every eligible pregnant woman and child attending these services does not get an ITN remains important and yet, unanswered.
METHODS
ANC and EPI issuing rates from seven countries were reviewed with the aim of conducting a blinded multi-country analysis. Monthly data from January to December 2021 was extracted from each country's health management information system and analysed jointly with a National Malaria Control Programme (NMCP) focal point. VectorLink CD assessment reports were also reviewed to glean key findings.
RESULTS
ITN issuing rates varied across countries at ANC (31% to 93%) and EPI (39% to 92%). Across the seven countries, the median ITN issuing rate was 64% at ANC and 78% at EPI. Results varied greatly across months per country at both ANC and EPI. NMCP focal points are aware that mass campaigns often negatively affect implementation of ITN distribution through ANC and EPI, even though global and national guidelines emphasize sustaining CD during campaigns. Concerns were also raised about the standard ITN issuing rate indicator at ANC and even more so at EPI due to the denominator. Findings from CD assessments were similar across countries: ITN stock was inconsistent and sometimes inadequate, and updated guidelines on ITN distribution and utilization and funding for social behaviour change activities were lacking at the facility level.
CONCLUSION
The importance of optimizing ANC and EPI routine channels cannot be underscored enough. They are at the frontline to protect the most biologically vulnerable populations, i.e., pregnant women and unborn and young children. Although there are encouraging signs of improvement in issuing rates with some countries reaching optimal rates, further improvements are needed to ensure that every pregnant woman and young child receives the ITN to which they are entitled.
Topics: Pregnancy; Child; Humans; Female; Child, Preschool; Prenatal Care; Immunization Programs; Awareness; Chlorphentermine
PubMed: 36461005
DOI: 10.1186/s12936-022-04373-6 -
Pulmonary Circulation 2018Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The...
Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the "serotonin hypothesis of pulmonary hypertension." Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1 (TPH1) is increased in patients with PAH and serotonin can act in a paracrine fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans, serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5-HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC contraction and proliferation via activation of downstream proliferative and contractile signaling pathways. Here we will review the current status of the serotonin hypothesis and discuss potential and novel therapeutic targets.
PubMed: 29468941
DOI: 10.1177/2045894018759125 -
Thorax Mar 1974, , 147-163. The ultrastructure of the bronchiolar Clara cell was examined in normal adult and neonatal rats, in similar animals which had been acutely exposed to...
, , 147-163. The ultrastructure of the bronchiolar Clara cell was examined in normal adult and neonatal rats, in similar animals which had been acutely exposed to hypoxia, and in adult rats following repeated doses of the anorexigen chlorphentermine. The Clara cell has all the features of a secretory cell, the product of secretion accumulating within smooth cisternae at the apex of the cell. The apical region is then extruded into the bronchiolar lumen in a process of apocrine secretion. Acute hypoxia accelerates this secretion in adult rats but has little effect upon neonatal rats. Administration of chlorphentermine induces a hyperplasia of Clara cells which is associated with large quantities of phospholipid free within the alveolar spaces and in macrophages. The Clara cells also contain accumulations of what appear to be phospholipid. This suggests that the Clara cell secretes the phospholipid pulmonary surfactant.
Topics: Animals; Animals, Newborn; Bronchi; Chlorphentermine; Cytoplasm; Endoplasmic Reticulum; Female; Golgi Apparatus; Hypoxia; Male; Microscopy, Electron; Phospholipids; Pulmonary Surfactants; Rats
PubMed: 4406652
DOI: 10.1136/thx.29.2.147 -
The West Africa ICEMR Partnerships for Guiding Policy to Improve the Malaria Prevention and Control.The American Journal of Tropical... Oct 2022The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up...
The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.
Topics: Animals; Anopheles; Chlorphentermine; Humans; Insecticides; International Cooperation; Malaria; Mali; Mosquito Vectors; Policy
PubMed: 36228908
DOI: 10.4269/ajtmh.21-1330 -
Thorax Sep 1973, , 559-566. Electron microscopy of lung tissue from rats treated with chlorphentermine shows an intense hyperplasia in the alveolar walls of granular pneumocytes which...
, , 559-566. Electron microscopy of lung tissue from rats treated with chlorphentermine shows an intense hyperplasia in the alveolar walls of granular pneumocytes which remain attached and do not migrate into the alveolar spaces. Numerous `foam cells' are found free in the alveoli and are histiocytes which have ingested osmiophilic lamellar bodies. Similar laminated inclusions are found in granular pneumocytes, membranous pneumocytes, bronchiolar Clara cells, pulmonary macrophages, and endothelial cells of pulmonary capillaries. The intra-alveolar debris is rich in osmiophilic lamellar bodies with associated phospholipid lattices. The appearances are those of a toxic alveolitis. Further studies of chronic toxicity are suggested to ascertain if this acute lesion progresses to fibrosing alveolitis.
Topics: Animals; Appetite Depressants; Chlorphentermine; Endothelium; Hyperplasia; Inclusion Bodies; Lung; Macrophages; Male; Microscopy, Electron; Phenethylamines; Pulmonary Alveoli; Rats
PubMed: 4361524
DOI: 10.1136/thx.28.5.559 -
Malaria Journal Jan 2024In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a...
Dynamics of malaria vector composition and Plasmodium falciparum infection in mainland Tanzania: 2017-2021 data from the national malaria vector entomological surveillance.
BACKGROUND
In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a periodical assessment of malaria vector composition and abundance, feeding and resting behaviours, and Plasmodium falciparum infection in different malaria epidemiological strata to guide the NMCP on the deployment of appropriate malaria vector interventions. This work details the dynamics of malaria vector composition and transmission in different malaria epidemiological strata.
METHODS
The MVES was conducted from 32 sentinel district councils across the country. Mosquitoes were collected by the trained community members and supervised by the NMCP and research institutions. Three consecutive night catches (indoor collection with CDC light trap and indoor/outdoor collection using bucket traps) were conducted monthly in three different households selected randomly from two to three wards within each district council. Collected mosquitoes were sorted and morphologically identified in the field. Thereafter, the samples were sent to the laboratory for molecular characterization using qPCR for species identification and detection of P. falciparum infections (sporozoites). ELISA technique was deployed for blood meal analysis from samples of blood-fed mosquitoes to determine the blood meal indices (BMI).
RESULTS
A total of 63,226 mosquitoes were collected in 32 district councils from January 2017 to December 2021. Out of which, 39,279 (62%), 20,983 (33%) and 2964 (5%) were morphologically identified as Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l., and as other Anopheles species, respectively. Out of 28,795 laboratory amplified mosquitoes, 13,645 (47%) were confirmed to be Anopheles arabiensis, 9904 (34%) as An. funestus sensu stricto (s.s.), and 5193 (19%) as An. gambiae s.s. The combined average entomological inoculation rates (EIR) were 0.46 (95% CI 0.028-0.928) for An. gambiae s.s., 0.836 (95% CI 0.138-1.559) for An. arabiensis, and 0.58 (95% CI 0.165-0.971) for An. funestus s.s. with variations across different malaria transmission strata. Anopheles funestus s.s. and An. arabiensis were predominant in the Lake and South-Eastern zones, respectively, mostly in high malaria transmission areas. Monthly mosquito densities displayed seasonal patterns, with two peaks following the rainy seasons, varying slightly across species and district councils.
CONCLUSION
Anopheles arabiensis remains the predominant vector species followed by An. funestus s.s. in the country. Therefore, strengthening integrated vector management including larval source management is recommended to address outdoor transmission by An. arabiensis to interrupt transmission particularly where EIR is greater than the required elimination threshold of less than one (< 1) to substantially reduce the prevalence of malaria infection.
Topics: Animals; Humans; Malaria; Anopheles; Plasmodium falciparum; Tanzania; Mosquito Vectors; Feeding Behavior; Malaria, Falciparum; Chlorphentermine
PubMed: 38243220
DOI: 10.1186/s12936-024-04849-7 -
British Journal of Clinical Pharmacology Apr 19771 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and...
1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed.
Topics: Adult; Biotransformation; Chemical Phenomena; Chemistry; Chlorobenzoates; Chlorphentermine; Humans; Hydrogen-Ion Concentration; Hydroxylation; Male; Oxidation-Reduction; Phentermine; Potassium Permanganate; Time Factors; Trifluoroacetic Acid; Trimethylsilyl Compounds
PubMed: 16634
DOI: 10.1111/j.1365-2125.1977.tb00693.x -
Toxicology and Applied Pharmacology Feb 1995Cationic amphiphilic drugs (CADs) are structurally characterized by hydrophobic ring structures and hydrophilic side chains. Studies have demonstrated that repeated... (Comparative Study)
Comparative Study
Cationic amphiphilic drugs (CADs) are structurally characterized by hydrophobic ring structures and hydrophilic side chains. Studies have demonstrated that repeated administration of CADs to experimental animals and humans may induce phospholipid (PL) accumulation within the cells of various tissues. The immunomodulatory azaspiranes are novel CADs with beneficial effects in a number of animal models of autoimmune disease and transplantation. Although the mechanism of action of these compounds is unclear, efficacy in all of the disease models is accompanied by the generation of suppressor cell (SC) activity in various lymphoid organs. SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine+ ++ hydrochloride) and two analogs, SK&F 106615 and SK&F 103811, were compared with chlorphentermine and chloroquine for their ability to induce PL accumulation and SC activity. Oral administration of SK&F 105685 and SK&F 106615 caused PL accumulation in bronchoalveolar lavage macrophages (AM) but to a far lesser extent (three- to fivefold) than chlorphentermine. Neither the immunologically unreactive azaspirane SK&F 103811 nor chloroquine affected PL levels. AM from rats treated with SK&F 105685 or SK&F 106615 expressed more potent SC activity than chlorphentermine. Thus, SC activity did not correlate with the extent of PL accumulation. Neither SK&F 103811 nor chloroquine induced SC activity. AM from SK&F 105685-treated rats had an enhanced ability to kill the opportunistic pathogen Candida albicans in vitro indicating that there was no impairment of macrophage-dependent host defense mechanisms.
Topics: Animals; Bronchi; Candida albicans; Chloroquine; Chlorphentermine; Immunosuppressive Agents; Inclusion Bodies; Macrophages, Alveolar; Male; Phospholipids; Pulmonary Alveoli; Rats; Rats, Inbred Lew; Spiro Compounds; Structure-Activity Relationship; T-Lymphocytes, Regulatory
PubMed: 7871542
DOI: 10.1006/taap.1995.1036