Low-field benchtop NMR spectroscopy: status and prospects in natural product analysis

Introduction: Since a couple of years, low-field (LF) nuclear magnetic resonance (NMR) spectrometers (40–100 MHz) have re-entered the market. They are used for various purposes including analyses of natural products. Similar to high-field instruments (300–1200 MHz), modern LF instruments can measure multiple nuclei and record two-dimensional (2D) NMR spectra. Objective: To review the commercial availability as well as applications, advantages, limitations, and prospects of LF-NMR spectrometers for the purpose of natural products analysis. Method: Commercial LF instruments were compared. A literature search was performed for articles using and discussing modern LF-NMR. Next, the articles relevant to natural products were read and summarised. Results: Seventy articles were reviewed. Most appeared in 2018 and 2019. Low costs and ease of operation are most often mentioned as reasons for using LF-NMR. Conclusion: As the spectral resolution of LF instruments is limited, they are not used for structure elucidation of new natural products but rather applied for quality control (QC), forensics, food and health research, process control and teaching. Chemometric data handling is valuable. LF-NMR is a rapidly developing niche and new instruments keep being introduced.</p

Early versus late initiation of GH replacement in adult-onset hypopituitarism

Introduction: Adult-onset growth hormone deficiency (AGHD) is usually the last deficiency to be substituted in hypopituitarism. In children with documented GH deficiency, treatment without delay is crucial for achieving optimal effects on growth and development. In adults, it is not known whether a delay in treatment initiation influences biochemical response and the favourable physiological effects resulting from GH replacement therapy (GHRT). Methods: A total of 1085 GH-deficient adults from KIMS (Pfizer International Metabolic Database) were included, adequately replaced with all pituitary hormones except for GH at baseline. Patients were stratified by sex and age (20–50 years and ≥50 years) and subsequently divided into two groups below and above the median duration of unsubstituted AGHD for that subgroup. The median time of unsubstituted GHD for the total cohort was 2.53 years (P5 = 0.35, P95 = 24.42). Results: Beneficial effects of 4 years of GHRT were observed on lipids and quality of life iall subgroups. A decrease in waist circumference was observed only in older (>50 years) patients. There was no difference in IGF-I SDS and in GH dose required to normalize IGF-I in patients with a duration of unsubstituted AGHD above or below the median. No relevant differences were found between the groups for anthropometric measures, cardiovascular risk factors and quality of life scores. Conclusion: In contrast to GHD in children and adolescents, no difference could be established in treatment response between early or late initiation of GHRT in AGHD in terms of required GH dose, IGF-I, metabolic health and quality of life

Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency

Objective: To compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis. Design: A post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses. Methods: Comparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day. Results: Out of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared. Conclusion: Patients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis