Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study.

Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable.

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.

Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022.

MiRNA-29b and miRNA-497 Modulate the Expression of Carboxypeptidase X Member 2, a Candidate Gene Associated with Left Ventricular Hypertrophy.

Left ventricular hypertrophy (LVH) is a major risk factor for adverse cardiovascular events. Recently, a novel candidate gene encoding the carboxypeptidase X member 2 (CPXM2) was found to be associated with hypertension-induced LVH. CPXM2 belongs to the M14 family of metallocarboxypeptidases, yet it lacks detectable enzyme activity, and its function remains unknown.

Availability of diagnostic services and essential medicines for non-communicable respiratory diseases in African countries.

The global burden of disease due to asthma and chronic obstructive pulmonary disease (COPD) is substantial and particularly great in low- and middle-income countries, including many African countries. Management is affected by availability of diagnostic tests and essential medicines. The study aimed to explore the availability of spirometry services and essential medicines for asthma and COPD in African countries.

Krill vs salps: dominance shift from krill to salps is associated with higher dissolved N:P ratios.

Pronounced atmospheric and oceanic warming along the West Antarctic Peninsula (WAP) has resulted in abundance shifts in populations of Antarctic krill and Salpa thompsoni determined by changes in the timing of sea-ice advance, the duration of sea-ice cover and food availability. Krill and salps represent the most important macrozooplankton grazers at the WAP, but differ profoundly in their feeding biology, population dynamics and stoichiometry of excretion products with potential consequences for the relative availability of dissolved nitrogen and phosphorus. Alternation of the dissolved nutrient pool due to shifts in krill and salp densities have been hypothesized but never explicitly tested by using observational data.

The impact of α-Lipoic acid on cell viability and expression of nephrin and ZNF580 in normal human podocytes.

Human podocytes (hPC) are essential for maintaining normal kidney function and dysfunction or loss of hPC play a pivotal role in the manifestation and progression of chronic kidney diseases including diabetic nephropathy. Previously, α-Lipoic acid (α-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of α-LA on hPC under non-diabetic conditions is unknown.

Multiple vs. single phytoplankton species alter stoichiometry of trophic interaction with zooplankton.

Despite the progress made in explaining trophic interactions through the stoichiometric interplay between consumers and resources, it remains unclear how the number of species in a trophic group influences the effects of elemental imbalances in food webs. Therefore, we conducted a laboratory experiment to test the hypothesis that multispecies producer assemblages alter the nutrient dynamics in a pelagic community. Four algal species were reared in mono- and polycultures under a 2 x 2 factorial combination of light and nutrient supply, thereby contrasting the stoichiometry of trophic interactions involving single vs.

Climate-driven extinctions shape the phylogenetic structure of temperate tree floras.

When taxa go extinct, unique evolutionary history is lost. If extinction is selective, and the intrinsic vulnerabilities of taxa show phylogenetic signal, more evolutionary history may be lost than expected under random extinction. Under what conditions this occurs is insufficiently known.

Epizooic metazoan meiobenthos associated with tubeworm and mussel aggregations from cold seeps of the northern Gulf of Mexico.

The abundance and higher taxonomic composition of epizooic metazoan meiobenthic communities associated with mussel and tubeworm aggregations of hydrocarbon seeps at Green Canyon, Atwater Valley, and Alaminos Canyon in depths between 1400 and 2800 m were studied and compared to the infaunal community of non-seep sediments nearby. Epizooic meiofaunal abundances of associated meiobenthos living in tubeworm bushes and mussel beds at seeps were extremely low (usually <100 ind. 10 cm(-2)), similar to epizooic meiofauna at deep-sea hydrothermal vents, and the communities were composed primarily of nematodes, copepods, ostracods, and halacarids.

ERK1/2-dependent contractile protein expression in vascular smooth muscle cells.

In vivo, vascular smooth muscle (VSM) cells change their contractile phenotype toward a more proliferative phenotype during the pathogenesis of vascular diseases. Because these dedifferentiated VSM cells may gradually regain contractile functions, we aimed to identify signaling pathways that result in an increased expression of contractile proteins in VSM cells. In vitro, serum and thrombin induced a reversible upregulation of smooth muscle myosin heavy-chain (SM-MHC) in cultured neonatal rat VSM cells.

Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid indicates differential cytosolic/nuclear localization.

Isotretinoin (13-cis-retinoic acid [13CRA], Accutane) is used for the treatment of dermatological diseases. Isotretinoin is, however, teratogenic in animals and humans. The mechanism of action of its teratogenicity is still not clearly identified.

Gbeta gamma mediate differentiation of vascular smooth muscle cells.

Proliferation and subsequent dedifferentiation of vascular smooth muscle (VSM) cells contribute to the pathogenesis of atherosclerosis and postangioplastic restenosis. The dedifferentiation of VSM cells in vivo or in cell culture is characterized by a loss of contractile proteins such as smooth muscle-specific alpha-actin and myosin heavy chain (SM-MHC). Serum increased the expression of contractile proteins in neonatal rat VSM cells, indicating a redifferentiation process.

Topical 9-cis-retinaldehyde for delivery of 9-cis-retinoic acid in mouse skin.

The 9-cis-retinoic acid (9cRA) is an endogenous ligand of retinoid X nuclear receptors (RXRs). Although the epidermis contains five times more RXRs than RARs, little is known on the activity of topical 9cRA. In order to circumvent surface isomerization of topically applied 9cRA into all-trans-retinoic acid (atRA), we used topical 9-cis-retinaldehyde (9cRAL) as a precursor of 9cRA, hypothesizing that keratinocytes would metabolize 9cRAL into 9-cis-retinoic acid (9cRA).

Retinoid signaling by all-trans retinoic acid and all-trans retinoyl-beta-D-glucuronide is attenuated by simultaneous exposure of human keratinocytes to retinol.

Retinol and retinyl esters are converted with time to slowly increasing amounts of all-trans retinoic acid (RA) in cultured human keratinocytes. Exogenous RA has been shown to limit retinol oxidation and to increase retinol esterification. Because significant amounts of retinol are present in biologic systems, we examined whether RA and all-trans-retinoyl-beta-D-glucuronide (RAG) interact with retinol in exhibiting their activities on HaCaT keratinocytes maintained in a retinoid-free culture system.

Metabolism of topical retinaldehyde and retinol by mouse skin in vivo: predominant formation of retinyl esters and identification of 14-hydroxy-4, 14-retro-retinol.

We have previously shown that retinaldehyde (RAL), a natural metabolite of beta-carotene and retinol (ROL), can be used topically in human skin and exerts biological activity; it may be a convenient way to deliver multipotential vitamin A activity in epidermis. RAL can be converted enzymatically into 2 pathways: one leads to ROL (and then retinyl esters), the other to retinoic acid (RA). The aim of the present study was 2-fold: (i) to see if RAL is metabolised in vivo when topically applied on mouse skin, and (ii) if so, to analyse the occurrence and relative importance of the 2 metabolic pathways as compared to ROL.

Stereoselective distribution of the teratogenic thalidomide analogue EM12 in the early embryo of marmoset monkey, Wistar rat and NMRI mouse.

Thalidomide administration during early gestation results in specific and dramatic limb defects in primates, but not in laboratory rodents such as the rat and mouse. The thalidomide analogue EM12 [2-(2,6-dioxopiperidine-3-yl)-phthalimidine] was used in the present study because this compound is metabolically more stable and teratogenically more potent than thalidomide in the monkey. We have administered the pure enantiomers, since we have previously shown that S-EM12 proved to be much more teratogenic in the monkey than R-EM12.

Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogenesis of anticonvulsant therapy.

The major antiepileptic drugs used for the control of seizures can induce developmental toxicity when administered during pregnancy. Vitamin A and retinoids are thought to control many processes of embryonic development including growth, differentiation and morphogenesis. We have therefore studied if the teratogenic action of antiepileptic agents could be mediated via alteration of the endogenous vitamin A--retinoid metabolism.

Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant's urine.

The effects of smoke exposure via mothers' milk and/or via passive smoking during the first year of life were investigated in a prospective longitudinal matched-pair study. The somatic and mental development of 69 infants whose mothers smoked more than five cigarettes per day throughout pregnancy and continued smoking after childbirth were compared with 69 children of non-smoking mothers. At birth, mean body weight of neonates from smoking mothers was significantly lower than the weight of neonates from non-smoking mothers.

The enantioselective teratogenicity of 2-n-propyl-4-pentynoic acid (4-yn-VPA) is due to stereoselective intrinsic activity and not differences in pharmacokinetics.

The present study was designed to investigate whether there are pharmacokinetic reasons for the enantioselective teratogenicity of R(+)-4-yn-VPA (low potency) and S(-)-4-yn-VPA (high potency). A gas chromatographic method was employed to determine 4-yn-VPA enantiomers in maternal plasma, brain, erythrocytes and in the embryo and decidua/extraembryonic membranes of the mouse following a single intraperitoneal dose of 300 mg/kg (+/-)-4-yn-VPA-Na on day 9 of gestation. Furthermore, the pharmacokinetics of R- and S-4-yn-VPA were studied in maternal plasma of day-8 pregnant mice following intraperitoneal administration of 300 and 500 mg (+/-)-4-yn-VPA-Na/kg body wt.

Sequences near the termini are required for transposition of the maize transposon Ac in transgenic tobacco plants.

Deletion derivatives of the maize transposable element Activator (Ac) were constructed in vitro and inserted into a kanamycin resistance gene. These constructions were then introduced into tobacco protoplasts derived from plants previously transformed with Ac. The ability of each deletion derivative to excise was measured by whether or not kanamycin-resistant tobacco calli were recovered.

Smoking and passive smoking during pregnancy and early infancy: effects on birth weight, lactation period, and cotinine concentrations in mother's milk and infant's urine.

The extent of smoke exposure via mother's milk and passive smoking was investigated in a prospective, longitudinal matched-pair study by comparison between children, whose mothers smoked substantially throughout pregnancy and nursing period and children whose mothers did not smoke. Our preliminary results show that not only infants of smoking mothers but also those of smoking fathers show reduction of birth weight. Smoking mothers weaned their babies earlier than non-smokers.