[(11) C]Carbon monoxide in labeling chemistry and positron emission tomography tracer development: scope and limitations.

[(11) C]Carbon monoxide is an attractive precursor for labeling carbonyl position in a wide range of organic compounds. The use of [(11) C]carbon monoxide in transition metal-mediated coupling reactions has been explored by several groups during the last 15 years, and an impressive number of the synthesis of [carbonyl-(11) C]compounds have been published to date. The application of radical-mediated [(11) C]carbonylation has also been explored in some extent. However, the main limitations to apply this potential precursor in (11) C-labeling chemistry are low concentration, poor solubility in commonly used organic solvents, and low reactivity. A couple of technical solutions such as high-pressure reactor system, microfluidic system, and different approaches to confine [(11) C]CO to the reaction media at ambient pressure have been developed over the years. Although considerable advances in [(11) C]carbon monoxide chemistry have been reported in recent years, its application in positron emission tomography tracer development is still an area of work in progress. This review summarizes all contributions to the area of radiolabeling using [(11) C]carbon monoxide published between 1995 and 2014 and discusses the scope and limitations of this method in clinical positron emission tomography tracer development.

An evaluation of a high-pressure (11)CO carbonylation apparatus.

[(11)C]Carbon monoxide ((11)CO) is a versatile building block for the synthesis of Positron Emission Tomography (PET) radioligands. However, the difficulty of trapping (11)CO in a small solvent volume has limited its utility. We here report an evaluation of a simple, fully automated high-pressure synthesizer prototype for the use in (11)C-carbonylation reactions. [(11)C]Carbon monoxide was easily prepared by online reduction of [(11)C]carbon dioxide using either Mo(s) or Zn(s) as the reducing agent. The conversion yield of (11)CO was >99% when zinc was used as the reducing agent, and the corresponding value for Mo was approximately 71%. When the Zn or Mo column was constantly kept under inert atmosphere, no significant decrease in reducing properties was observed for more than 100 (11)CO productions. However, in our hands, Mo reductant was much easier to service. A total of nine functional groups were successfully radiolabeled using the (11)CO synthesizer prototype. All measured radiochemical yields exceeded 37%, and the (11)CO trapping efficiency was generally above 90%, except for the Suzuki coupling where the trapping efficiency was 80%. This high-pressure synthesizer using [(11)C]carbon monoxide as the labeling precursor is easy to operate allowing for (11)C-carbonylation reactions to be performed in a high yield and in a routinely fashion.

Exploring the reproductive features of Clupisoma garua from Ganges River, Bangladesh: insights into eco-climatic factors for sustainable management and advancements in aquaculture practices.

The Garua bacha, Clupisoma garua, holds considerable commercial and nutritional significance as a fish species. This study investigates the relationships between GSI (gonadosomatic index) and eco-climatic conditions, and provides comprehensive insights into several facets of reproduction, such as size at first sexual maturity (Lm), spawning season, peak spawning period, and proposes sustainable management strategies for C. garua in the Ganges River, northwestern, Bangladesh. Since January to December 2017, 570 female individuals have been gathered from the Ganges River using cast nets, gill nets, and square lift nets on a monthly basis. The total length (TL) of the specimens varied from 3.90 to 26.30 cm. Lm was estimated as 14.30 cm based on the results of the TL vs. GSI, MGSI (modified gonadosomatic index), DI (Dobriyal index), 14.00 cm through TL-FL regressions, and 15.18 cm depending on Lmax for this species. Furthermore, the spawning period was observed from May to August, peaking in June and July, based on greater GSI, MGSI, and DI values. Throughout the peak spawning season, there was not a significant differ from a value of 100 in the relative weight (WR) of the female species. During the spawning season, a substantial association between temperature and GSI (p = 0.0038); rainfall and GSI (p = 0.0043); DO and GSI (p = 0.0043); pH and GSI (p = 0.0002); and alkalinity and GSI (p = 0.0001) was detected. Analyzing a 55-year data series (1964-2018), it became clear that an increase in average air temperature of 0.0289 °C and a decrease in rainfall of 2.988 mm per year might possibly delay the spawning season of this species. As a consequence, the results of this study provide crucial information for developing management strategies to safeguard C. garua populations in the Ganges River and its adjacent ecosystems.

Estimating the growth parameters, exploitation rate, biomass and maximum sustainable yield of long whisker catfish Mystus gulio (Hamilton, 1822) in the coastal waters from southwestern Bangladesh.

The research provides a comprehensive analysis of Mystus gulio including growth pattern, growth parameters, recruitment patterns, mortality rates, biomass, exploitation rate (E), and the estimation of maximum sustainable yield (MSY) within the southwestern coastal waters of Bangladesh. From January to December 2017, fishers provided around 1200 specimens. FAO-ICLARM Stock Assessment Tool and Excel-add-in-solver were used to assess stock status through length-frequency data. Indeed, the research findings indicated that the population of M. gulio displayed negative allometric for both individuals (b = 2.53 for male, b = 2.50 for female), as demonstrated by the calculated allometric coefficient value. Nonetheless, the population's dynamic characteristics revealed an asymptotic length (L∞) of 19.34 cm, 23.28 cm and growth coefficient (K) 0.94 year-1 and 0.81 year-1 for male and female M. gulio. The growth performance indexes (Ø') of 2.55 and 2.64 for male and female and maximum lifespan (tmax) 3.20 years and 3.70 years respectively. This study revealed that the slightly variations in the natural mortality rate (M) for both specimens at 1.55 year-1 and 1.59 year-1. The fishing mortality rate (F) 2.75 year-1 and 1.98 year-1and total mortality rate (Z) 4.30 year-1 and 3.57 year-1 for male and females, respectively. The maximum permissible exploitation rate (Emax = 0.421) was lower than the actual exploitation rate (E = 0.63). The MSY was calculated at 67.968 metric tons. Without a doubt, overfishing stands out as the most critical threat to the wild stock. Therefore, it is clear that the existing fishing approach was not efficiently managed the standing stock in a sustainable manner. The findings would be useful for established proper fishing regulations in coastal waters and the surrounding ecosystems.

Investigation of CeO2 nanoparticles on the performance enhancement of InsulatingOils.

Integrating nanotechnology in dielectric fluid significantly inhibits losses and boosts overall dielectric fluid performance. There has been research done on the effects of introducing various nanoparticles, such as titania, alumina, silica nanodiamonds, etc. In this paper, a novel nanoparticle, Ceria (CeO2), has been used, and its properties were examined using the FTIR (Fourier Transform Infrared) spectrum, the XRD (X-ray Diffraction) spectrum, the SEM (Scanning Electron Microscopy), and the TEM (Transmission Electron Microscopy). This paper illustrates an efficient dielectric fluid prepared by the successful dispersion of Cerium Oxide (CeO2) nanoparticles in various concentrations into four commercial oils, namely mineral oil, rapeseed oil, synthetic ester oil, and soybean oil, to enhance and improve their dielectric characteristics. The performance investigation emphasises breakdown strength enhancement and other dielectric properties of the colloidal solution comprising different nanoparticle (NP) concentrations. Various commercial oils are used as a base in nano-oil to diversify their applicability as dielectric fluids by measuring the correlation in dielectric parameters and statistically assessing their applicability with normal and Weibull distributions. The obtained experimental data sets were analyzed using the Statistics and Machine Learning Toolbox in MATLAB. The aging measurement has been done only on mineral oil, and results were matched using a predictive model of statistics and the Machine Learning Toolbox in MATLAB. Well-dispersed CeO2 NPs in the insulating oils lead to a significant increase in AC breakdown strength. The effect of ageing on the dielectric properties of nano oils yields better results than conventionally aged oil. It has been observed that the breakdown voltage is enhanced by up to 30% for mineral oil at an optimal concentration of 0.01 g/L, 9% for synthetic ester oil at 0.03 g/L, 18% for rapeseed oil at 0.02 g/L, and 19% for soybean oil at 0.03 g/L nanoparticle concentration. Following the dispersion of CeO2 nanoparticles, the dielectric constant of all insulating oils has also significantly improved. The overall experimental results are promising and show the potential of the CeO2 NPs-based nano oil as an efficient and highly performing dielectric oil for different power applications.

First report on population dynamics and stock status of Badis badis in a wetland ecosystem (NW Bangladesh): Insights from new recorded maximum length.

Badis badis (Hamilton, 1822) is a popular ornamental fish species in the world. This study provides valuable insights into some biological indices of B. badis using a sample of 293 individuals. These individuals were captured from June 2021 to May 2022 using several traditional fish harvesting gears and traps in the Babu Mondoler beel, a wetland ecosystem in NW Bangladesh. Biometric data were collected for each individual, contributing to a comprehensive understanding of this species. The recorded results revealed a wide range of total length (TL), varying from 2.30 to 11.33 cm. Notably, we observed a maximum length of 11.33 cm TL and a maximum body weight (BW) of 18.18 g, ranging from 0.20 to 18.18 g, setting a new record and showcasing the diversity in size within the population. The estimated allometric coefficient (b) showed that combined sexes had negative allometric growth (b = 2.67). Growth parameters were assessed as L∞ = 11.93 cm, K = 0.95 year-1 and Ø' = 2.13. The tmax was 3.16 years. The Lm was measured at 7.02 cm TL and tm = 0.89 year. In this study, KF (1.4240 ± 0.3194) was best for the wellbeing of B. badis in the study area. The a3.0 was estimated at 0.0079 and the relative weight WR (100.90 ± 16.994). Physiological status showed that maximum fatty fish were observed at 10.00-12.00 cm TL; lowest at 4.0-6.00 cm TL. Moreover, the Z, Mw, F and E were estimated to be 3.29 year-1, 1.45 year-1, 1.84 year-1and 0.56, respectively. Additionally, the Lopt for this species was found to be 7.91 cm TL. The findings from this study hold great potential for enhancing the assessment and management of the specimen in the study area and its ecological community. These valuable insights into the population parameters, growth patterns, and exploitation rates of B. badis can inform future management strategies, ensuring the sustainable utilization of this fishery resource in Bangladesh and others neighboring countries.

Estimation of life history parameters for river catfish Eutropiichthys vacha: insights from multi-models for sustainable management.

The river catfish, Eutropiichthys vacha is a vital protein source for rural communities and has high commercial value, but understanding its life history and management strategies reveals major inadequacies and ambiguities in the riverine ecosystems. Consequently, this study employs multi-models to analyze the life history parameters of E. vacha in the Ganges River (northwestern Bangladesh) from January to December, 2020. The total length (TL) and body weight (BW) of 362 individuals (male = 170, female = 192) were measured by a measuring board and a digital weighing balance, respectively. The overall sex ratio (male: female) was 1.0: 1.13 and did not oscillate statistically from the standard 1:1 ratio (p > 0.05). The TL varied from 6.7-19.2 cm for males and 6.3-19.0 cm for females. The length-frequency distributions (LFDs) revealed females outnumbered in 8.0-9.99 cm TL whereas males in 7.0-7.99 cm TL. The slope (b) of the length-weight relationship (TL vs. BW) for both sexes (b = 2.87) was substantially lower than isometry, specifying negative allometric growth pattern for E. vacha. Sex-specific relative (K R ) and Fulton's (K F ) condition analysis revealed better state of well-being of males than females. Only K F exhibited significant correlation with both BW and TL, hence making it ideal condition for predicting the fitness of E. vacha in this river. Moreover, the relative weight (W R ) suggests an imbalanced habitat for females with higher abundance of predators but suitable for males. The form factor (a 3.0 ) was 0.0062 and 0.0065, whereas the size at first maturity (L m ) and mean natural mortality (M W ) were 11.38 and 11.27 cm TL and 1.29 and 1.28 year-1 for the respective sexes. Besides, the calculated mean optimum catchable length (L opt ) was 13.58 and 13.09 cm TL for each sex. These findings will be crucial for further studies and to recommend appropriate strategy for the sustainable management of E. vacha in the Ganges River and adjacent watersheds.

A Review Of Preclinical Tools To Validate Anti-Diarrheal Agents.

BACKGROUND: Since their inception, preclinical experimental models have played an important role in investigating and characterizing disease pathogenesis. These in vivo, ex vivo, and in vitro preclinical tests also aid in identifying targets, evaluating potential therapeutic drugs, and validating treatment protocols. INTRODUCTION: Diarrhea is a leading cause of mortality and morbidity, particularly among children in developing countries, and it represents a huge health-care challenge on a global scale. Due to its chronic manifestations, alternative anti-diarrheal medications must be tested and developed because of the undesirable side effects of currently existing anti-diarrheal drugs. METHODS: Several online databases, including Science Direct, PubMed, Web of Science, Google Scholar and Scopus, were used in the literature search. The datasets were searched for entries of studies up to May, 2022. RESULTS: The exhaustive literature study provides a large number of in vivo, in vitro and ex vivo models, which have been used for evaluating the mechanism of the anti-diarrheal effect of drugs in chemically-, pathogen-, disease-induced animal models of diarrhea. The advances and challenges of each model were also addressed in this review. CONCLUSION: This review encompasses diverse strategies for screening drugs with anti-diarrheal effects and covers a wide range of pathophysiological and molecular mechanisms linked to diarrhea, with a particular emphasis on the challenges of evaluating and predictively validating these experimental models in preclinical studies. This could also help researchers find a new medicine to treat diabetes more effectively and with fewer adverse effects.

Reproductive performance of Asian stinging catfish Heteropneustes fossilis (Bloch 1794) in the Ganges River (NW Bangladesh) in relation to environmental factors.

Reproduction plays an important role in fish population efficiency and its resiliency to fishing and environment changes. The present study described the comprehensive information on reproductive feature of stinging catfish, Heteropneustes fossilis (Bloch 1794), including size at sexual maturity, spawning season, and fecundity using 622 female individuals sampling by the use of gill net, cast net, and square lift net from January to December 2019 in the Ganges River. We calculated the influences of various environmental parameters which include temperature, dissolved oxygen, pH, and rainfall on the reproductive feature of H. fossilis in the Ganges River. For every specimen, total length (TL), standard length (SL), and body weight (BW) were estimated by measuring board and electronic weighing scale. With ventral dissection of fishes, female gonads were cautiously removed and measured to 0.01 g precision. The gonadosomatic index (GSI), modified gonadosomatic index (MGSI), and Dobriyal index (DI) were used to assess the size at sexual maturity (Lm) and spawning season. According to the results of these indices, Lm was obtained 15.5 cm in TL. Also, TL50 was determined through logistic function as 15.5 cm in TL. Moreover, the highest GSI, MGSI, and DI values indicated the spawning season as of March-August, with peak in May-June. Total fecundity (FT) varied from 2059 to 59,984 with a mean of 25,028 ± 15,048. Temperature and rainfall was statistically correlated with GSI. In addition, long climatic data series analysis denoted that yearly mean atmospheric temperature is rising in 0.028 °C/year and yearly mean rainfall is declining in 2.98 mm/year which may suggest a potential shift of the spawning period of the species in the future if this trend persists. The results of our study might be more useful in imposing particular management and conservation for H. fossilis in the Ganges River and the surroundings.

Infection control teams for reducing healthcare-associated infections in hospitals and other healthcare settings: a protocol for systematic review.

INTRODUCTION: Healthcare-associated infections (HCAIs) are a worldwide problem. Infection control in hospitals is usually implemented by an infection control team (ICT). Initially, ICTs consisted of doctors, nurses, epidemiologists and microbiologists; then, in the 1980s, the infection control link nurse (ICLN) system was introduced. ICTs (with or without the ICLN system) work to ensure the health and well-being of patients and healthcare professionals in hospitals and other healthcare settings, such as acute care clinics, community health centres and care homes. No previous study has reported the effects of ICTs on HCAIs. This systematic review aims to assess the effectiveness of ICTs with or without the ICLN system in reducing HCAIs in hospitals and other healthcare settings. METHODS AND ANALYSIS: We will perform a comprehensive literature search for randomised controlled trials in four databases: PubMed, Embase, CINAHL and the Cochrane Library. The primary outcomes are: patient-based/clinical outcomes (rate of HCAIs, death due to HCAIs and length of hospital stay) and staff-based/behavioural outcomes (compliance with infection control practices). The secondary outcomes include the costs to the healthcare system or patients due to extended lengths of stay. Following data extraction, we will assess the risk of bias by using the Cochrane Effective Practice and Organization of Care risk of bias tool. If data can be pooled across all the studies, we will perform a meta-analysis. ETHICS AND DISSEMINATION: We will use publicly available data, and therefore, ethical approval is not required for this systematic review. The findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CRD42020172173.

Trends and projections of under-5 mortality in Bangladesh including the effects of maternal high-risk fertility behaviours and use of healthcare services.

OBJECTIVE: This study examines trends and puts forward projections of under-5 mortality (U5M) in Bangladesh and identifies the effects of maternal high-risk fertility behaviours and use of healthcare services. METHODS: Data from seven waves of the Bangladesh Demographic and Health Survey (1994-2014) were analyzed for trends and projections of U5M and a Chi-square (χ2) test was used to identify if there was any association with maternal high-risk fertility behaviours and use of healthcare services. A multivariate logistic regression model was used to determine the effects of fertility behaviors and healthcare usage on the occurrence of U5M adjusting with confounders. RESULTS: U5M declined from 82.5 to 41.0 per 1000 livebirths during 1994-2014 and is projected to further reduce to 17.6 per 1000 livebirths by 2030. The study identified a noticeable regional variation in U5M with maternal high-risk fertility behaviours including age at birth <18 years (aOR: 1.84, 95% CI: 1.23-2.76) and birth interval <24 months (aOR: 1.56, 95% CI: 1.02-2.37) found to be significant determinants. There was a 39-53% decline in this rate of mortality among women that had used antenatal care services at least four times (aOR, 0.51, 95% CI: 0.27-0.97), delivery care (aOR, 0.47, 95% CI: 0.24-0.95), and had received postnatal care (aOR, 0.61, 95% CI: 0.41-0.91) in their last birth. Cesarean section was found to be associated with a 51% reduction in U5M (aOR, 0.49, 95% CI: 0.29-0.82) compared to its non-use. CONCLUSION: The Sustainable Development Goals require a U5M rate of 25 per 1000 livebirths to be achieved by 2030. This study suggests that with the current trend of reduction, Bangladesh will achieve this target before the deadline. This study also found that maternal high-risk fertility behaviours and non-use of maternal healthcare services are very prevalent in some regions of Bangladesh and have increased the occurrence of U5M in those areas. This suggests therefore, that policies and programmes designed to reduce the pregnancy rates of women that are at risk and to encourage an increase in the use of maternal healthcare services are needed.

Stock assessment of Hooghly Croaker Panna heterolepis in the Bay of Bengal (Southern Bangladesh): implications for sustainable management.

The study describes growth pattern, growth parameter, mortality, recruitment pattern, exploitation rate (E) and maximum sustainable yield (MSY) to Panna heterolepis from the Bay of Bengal (Bangladesh). About 1223 specimens were collected from commercial fishermen for 12 consecutive months from January to December, 2019. Length-frequency data were analyzed with FAO-ICLARM Stock Assessment Tool. Moreover, our study recorded different water quality and environmental parameters including pH, rainfall, temperature and DO (dissolved oxygen) from the Bay of Bengal. The findings of the study revealed that the allometric co-efficient (b) value indicated negative allometric growth (<3.00) for P. heterolepis population. Whereas, the population dynamic parameters showed growth coefficient (K) 0.13 year-1, life-span (t max ) 3.85 year and growth performance index (Ø') 2.30. Along with this, P. heterolepis was found to grow rapidly with an asymptotic length (L ∞) of 39.08 cm. We found that the natural mortality (M =0.44 year-1) rate was almost similar with fishing mortality (F = 0.42 year-1). Consequently, the standing stock was not quite sustainable with the existing fishing strategy. Furthermore, the maximum allowable exploitation rate (E max = 0.471) was lower than the recorded exploitation rate (E = 0.490). Subsequently, overfishing is the most focal threat to the wild stock. The recruitment pattern was almost continuous throughout sampling period. Finally, the MSY was assessed at 10234.47 metric tons. Additionally, the environmental parameters denoted that the ecosystem was in a balanced condition for the wild population. The findings would be very useful to introduce appropriate fishing regulations in the Bay of Bengal and nearby ecosystem.

Macroamphiphilic components of thermophilic actinomycetes: identification of lipoteichoic acid in Thermobifida fusca.

The cell envelopes of gram-positive bacteria contain structurally diverse membrane-anchored macroamphiphiles (lipoteichoic acids and lipoglycans) whose functions are poorly understood. Since regulation of membrane composition is an important feature of adaptation to life at higher temperatures, we have examined the nature of the macroamphiphiles present in the thermophilic actinomycetes Thermobifida fusca and Rubrobacter xylanophilus. Following hot-phenol-water extraction and purification by hydrophobic interaction chromatography, Western blotting with a monoclonal antibody against lipoteichoic acid strongly suggested the presence of a polyglycerophosphate lipoteichoic acid in T. fusca. This structure was confirmed by chemical and nuclear magnetic resonance analyses, which confirmed that the lipoteichoic acid is substituted with beta-glucosyl residues, in common with the teichoic acid of this organism. In contrast, several extraction methods failed to recover significant macroamphiphilic carbohydrate- or phosphate-containing material from R. xylanophilus, suggesting that this actinomycete most likely lacks a membrane-anchored macroamphiphile. The finding of a polyglycerophosphate lipoteichoic acid in T. fusca suggests that lipoteichoic acids may be more widely present in the cell envelopes of actinomycetes than was previously assumed. However, the apparent absence of macroamphiphiles in the cell envelope of R. xylanophilus is highly unusual and suggests that macroamphiphiles may not always be essential for cell envelope homeostasis in gram-positive bacteria.

Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport.

Species differences occur in the brain concentrations of drugs, but the reasons for these differences are not yet apparent. This study was designed to compare brain uptake of three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain concentrations and brain-to-plasma ratios were compared; [(11)C]verapamil in rats, guinea pigs, and monkeys; [(11)C](S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino)-2(S)-phenylpiperidine (GR205171) in rats, guinea pigs, monkeys, and humans; and [(18)F]altanserin in rats, minipigs, and humans. The fraction of the unbound radioligand in plasma was studied along with its metabolism. The effect of P-gp inhibition was investigated by administering cyclosporin A (CsA). Pronounced species differences were found in the brain and brain-to-plasma concentrations of [(11)C]verapamil, [(11)C]GR205171, and [(18)F]altanserin with higher brain distribution in humans, monkeys, and minipigs than in rats and guinea pigs. For example, the brain-to-plasma ratio of [(11)C]GR205171 was almost 9-fold higher in humans compared with rats. The species differences were still present after P-gp inhibition, although the increase in brain concentrations after P-gp inhibition was somewhat greater in rats than in the other species. Differences in plasma protein binding and metabolism did not explain the species-related differences. The findings are important for interpretation of brain drug delivery when extrapolating preclinical data to humans. Compounds found to be P-gp substrates in rodents are likely to also be substrates in higher species, but sufficient blood-brain barrier permeability may be retained in humans to allow the compound to act at intracerebral targets.

[(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology.

PURPOSE: [(11)C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [(11)C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[(18)F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging. METHOD: We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs. RESULTS: C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity. CONCLUSION: 2-[(18)F]Fluoroacetate cannot be regarded as a functional analogue of 1-[(11)C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.

Synthesis of ([(11)C]carbonyl)raclopride and a comparison with ([(11)C]methyl)raclopride in a monkey PET study.

INTRODUCTION: The selective dopamine D2 receptor antagonist raclopride is usually labeled with carbon-11 using [(11)C]methyl iodide or [(11)C]methyl triflate for use in the quantification of dopamine D2 receptors in human brain. The aim of this work was to label raclopride at the carbonyl position using [(11)C]carbon monoxide chemistry and to compare ([(11)C]carbonyl)raclopride with ([(11)C]methyl)raclopride in non-human primate (NHP) using PET with regard to quantitative outcome measurement, metabolism of the labeled tracers and protein binding. METHODS: Palladium-mediated carbonylation using [(11)C]carbon monoxide, 4,6-dichloro-2-iodo-3-methoxyphenol and (S)-(-)-2-aminomethyl-1-ethylpyrrolidine was applied in the synthesis of ([(11)C]carbonyl)raclopride. The reaction was performed at atmospheric pressure using xantphos as supporting phosphine ligand and palladium (π-cinnamyl) chloride dimer as the palladium source. ([(11)C]Methyl)raclopride was prepared by a previously published method. In the PET study, two female cynomolgus monkeys were used under gas anesthesia of sevoflurane. A dynamic PET measurement was performed for 63 min with an HRRT PET camera after intravenous injection of ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride, respectively, during the same day. The order of injection of the two PET radioligands was changed between the two monkeys. The venous blood sample for measurement of protein binding was taken 3 min prior to the PET scan. Binding potential (BPND) of the putamen and caudate was calculated with SRTM using the cerebellum as a reference region. RESULTS: The target compound ([(11)C]carbonyl)raclopride was obtained with 50 ± 5% decay corrected radiochemical yield and 95% radiochemical purity. The trapping efficiency (TE) of [(11)C]carbon monoxide was 65 ± 5% and the specific radioactivity of the final product was 34 ± 1 GBq/µmol after a 50 min of synthesis time. The radiochemical yield of ([(11)C]methyl)raclopride was in the same range as published previously i. e. 50-60% and specific radioactivity of those two batches which were used in the present PET study were 192 GBq/µmol and 638 GBq/µmol respectively after a synthesis time of 32 min. In monkey PET studies, the percentage difference of BPND in putamen was <3% and that in caudate was <9% for the two radioligands. The plasma protein binding was 86.2 ± 0.3% and 85.7 ± 0.6% for ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride, respectively. The radiometabolite pattern was similar for both radioligands. CONCLUSION: Raclopride was (11)C-labeled at the carbonyl position using a palladium-mediated [(11)C]carbonylation reaction. A comparison between ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride with regard to quantitative PET outcome measurements, metabolism of radioligands and protein binding in monkey was performed. The monkey PET study with ([(11)C]carbonyl)raclopride showed similar results as for ([(11)C]methyl)raclopride. The PET studies were performed on 2 subjects.

Preclinical studies of potential amyloid binding PET/SPECT ligands in Alzheimer's disease.

Visualizing the neuropathological hallmarks amyloid plaques and neurofibrillary tangles of Alzheimer's disease in vivo using positron emission tomography (PET) or single photon emission computed tomography will be of great value in diagnosing the individual patient and will also help in our understanding of the disease. The successful introduction of [(11)C]PIB as a PET tracer for the amyloid plaques less than 10 years ago started an intensive research, and numerous new compounds for use in molecular imaging of the amyloid plaques have been developed. The candidates are based on dyes like thioflavin T, Congo red and chrysamine G, but also on other types such as benzoxazoles, curcumin and stilbenes. In the present review, we present methods of the radiochemistry and preclinical evaluation as well as the main properties of some of these compounds.

Lipoteichoic acid biosynthesis: two steps forwards, one step sideways?

Lipoteichoic acids (LTAs) are membrane-anchored molecules in the cell envelopes of Gram-positive bacteria. Until recently, they were considered to be restricted to the Firmicutes, which include important pathogens such as Staphylococcus aureus and Streptococcus pneumoniae. Polyanionic LTAs have fundamentally important roles in divalent cation retention within the Gram-positive cell envelope and thereby influence bacterial cell division. Thus, LTA biosynthesis provides an attractive target for the development of novel antimicrobial interventions. Recent studies, notably two investigations of S. aureus and another of Bacillus subtilis, have greatly improved our understanding of the genetic basis of LTA biosynthesis. In addition, reports have revealed that at least some members of the Actinobacteria (another phylum of Gram-positive bacteria) produce LTAs, rather than the lipoglycans previously assumed to be typical of this taxon. The availability of whole bacterial genome sequences has enabled us to perform comparative analyses to shed light on the distribution of putative LTA biosynthetic genes among bacteria. Here, we discuss the results of these genomic analyses, together with the current literature, and propose that LTA biosynthesis in Actinobacteria might be fundamentally different to that in most Firmicutes.

Pharmacokinetics of P-glycoprotein inhibition in the rat blood-brain barrier.

This article describes the experimental set-up and pharmacokinetic modeling of P-glycoprotein function in the rat blood-brain barrier using [(11)C]verapamil as the substrate and cyclosporin A as an inhibitor of P-gp. [(11)C]verapamil was administered to rats as an i.v. bolus dose followed by graded infusions to obtain steady-state concentrations in the brain during 70 min. CsA was administered as a bolus followed by a constant infusion 20 min after the start of the [(11)C]verapamil infusion. The brain uptake of [(11)C]verapamil over 2 h was portrayed in a sequence of PET scans in parallel with measurement of [(11)C]verapamil concentrations in blood and plasma and CsA concentrations in blood. Mixed effects modeling in NONMEM was used to build a pharmacokinetic model of CsA-induced P-gp inhibition. The brain pharmacokinetics of [(11)C]verapamil was well described by a two-compartment model. The effect of CsA on the uptake of [(11)C]verapamil in the brain was best described by an inhibitory indirect effect model with an effect on the transport of [(11)C]verapamil out of the brain. The CsA concentration required to obtain 50% of the maximal inhibition was 4.9 microg/mL (4.1 microM). The model parameters indicated that 93% of the outward transport of [(11)C]verapamil was P-gp mediated.

Synthesis of [11C]/(13C)amines via carbonylation followed by reductive amination.

Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by reductive amination. The 11C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or aryl triflates, [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in this step were then transformed directly into amines by reductive amination using different amines in the presence of TiCl4 and NaBH3CN. The 11C-labelled amines were obtained with decay-corrected radiochemical yields in the range 2-78%. The radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl-phenyl-amine was synthesised and analysed by NMR spectroscopy for confirmation of the labelling position. Specific radioactivity was determined for the same compound. The reference compounds were prepared by reductive amination of ketones using conventional reaction conditions and three of the compounds were novel. The presented approach is a new method for the synthesis of [11C]/(13C)amines.