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The Surgical Clinics of North America Aug 2024Primary hyperparathyroidism (PHPT) is caused by the overproduction of parathyroid hormone by 1 or more parathyroid glands resulting in hypercalcemia and its downstream... (Review)
Review
Primary hyperparathyroidism (PHPT) is caused by the overproduction of parathyroid hormone by 1 or more parathyroid glands resulting in hypercalcemia and its downstream clinical consequences. The definitive management of PHPT is surgery. Approaches to successful surgery include bilateral exploration or focused parathyroidectomy with intraoperative parathyroid hormone monitoring, which in experienced hands are both associated with a low risk of complications.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Primary; Parathyroid Hormone
PubMed: 38944500
DOI: 10.1016/j.suc.2024.02.009 -
The Surgical Clinics of North America Aug 2024Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple... (Review)
Review
Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Parathyroid Neoplasms; Parathyroid Hormone; Hypercalcemia; Adenoma
PubMed: 38944499
DOI: 10.1016/j.suc.2024.02.008 -
Advances in Pediatrics Aug 2024To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the... (Review)
Review
To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the various forms of neonatal hypoglycemia and discusses their implications for newborn care. Evidence indicates that all of the major forms of neonatal hypoglycemia are the result of hyperinsulinism due to dysregulation of pancreatic islet insulin secretion. Based on these observations, the authors propose that routine measurement of B-hydroxybutyrate should be considered an essential part of glucose monitoring in newborn infants.
Topics: Humans; Infant, Newborn; Hypoglycemia; Blood Glucose; Insulin; Hyperinsulinism
PubMed: 38944478
DOI: 10.1016/j.yapd.2024.03.001 -
Protein Expression and Purification Jun 2024Peptides are used for diagnostics, therapeutics, and as antimicrobial agents. Most peptides are produced by chemical synthesis, but recombinant production has recently...
Peptides are used for diagnostics, therapeutics, and as antimicrobial agents. Most peptides are produced by chemical synthesis, but recombinant production has recently become an attractive alternative due to the advantages of high titers, less toxic waste and correct folding of tertiary structure. Somatostatin-28 is a peptide hormone that regulates the endocrine system, cell proliferation and inhibits the release of numerous secondary hormones in human body. It is composed of 28 amino acids and has one disulfide bond, which makes it to an optimal model peptide for a whole downstream purification process. We produced the peptide in the periplasm of E. coli using the CASPON™ technology, an affinity fusion technology system that enables high soluble expression of recombinant proteins and cleaves the fusion tag with a circularly permuted human caspase-2. Furthermore, purification of the products is straight forward using an established platform process. Two different case studies for downstream purification are presented, starting with either hydrochloric acid or polyethyleneimine as an extraction aid. After release of affinity-tagged somatostatin-28 out of E. coli's periplasm, several purification steps were performed, delivering a pure peptide solution after the final polishing step. The process was monitored by reversed-phase high-performance liquid chromatography as well as mass spectrometry to determine the yield and correct disulfide bond formation. Monitoring of impurities like host cell proteins, DNA and endotoxins after each downstream unit confirmed effective removal for both purification pathways.
PubMed: 38944221
DOI: 10.1016/j.pep.2024.106537 -
International Journal of Pharmaceutics Jun 2024Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone... (Review)
Review
Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancreatic β-cells. Insulin is highly sensitive to environmental stresses and readily undergoes structural changes, being also able to unfold and aggregate in physiological conditions. Even; small changes altering the structural integrity of insulin may have significant impacts on its biological efficacy to its physiological and pharmacological activities. Insulin analogs have been engineered to achieve modified properties, such as improved stability, solubility, and pharmacokinetics, while preserving the molecular pharmacology of insulin. The casually or purposively strategies of chemical modifications of insulin occurred to improve its therapeutic and pharmaceutical properties. Knowing the effects of chemical modification, formation of aggregates, and nanoparticles on protein can be a new look at the production of protein analogues drugs and its application in living system. The project focused on effects of chemical modifications and nanoparticles on the structure, stability, aggregation and their results in effective drug delivery system, biological activity, and pharmacological properties of insulin. The future challenge in biotechnology and pharmacokinetic arises from the complexity of biopharmaceuticals, which are often molecular structures that require formulation and delivery strategies to ensure their efficacy and safety.
PubMed: 38944170
DOI: 10.1016/j.ijpharm.2024.124399 -
Peptides Jun 2024This paper is the forty-sixth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles... (Review)
Review
This paper is the forty-sixth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2023 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug and alcohol abuse (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).
PubMed: 38943841
DOI: 10.1016/j.peptides.2024.171268 -
Nigerian Journal of Clinical Practice Jun 2024Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase...
BACKGROUND
Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase exercise capacity.
AIMS
In this study, the effect of metformin administered in combination with exercise on osteocalcin (OCN), insulin, and interleukin-6 (IL-6) levels in rats was investigated.
METHODS
Forty-two male Wistar rats were used in this study. The animals were randomly divided into six groups: control (CONT), only exercise (EXE), metformin_100 mg/kg (Met100), metformin_200 mg/kg (Met200), metformin_100 mg/kg+exercise (Met100+EXE), and metformin_200 mg/kg+exercise (Met200+EXE). A 10-week intervention was conducted, excluding exercise training. During the experiment, the groups receiving metformin application (100 or 200 mg/kg) were administered with metformin. At the end of the study, serum samples were collected from the rats to determine the levels of osteocalcin, insulin, and IL-6 using the enzyme-linked immunosorbent assay method. In addition, glucose levels and body weights were evaluated. GraphPad Prism was used for the analyses.
RESULTS
The OCN and insulin levels of the Met100+EXE and Met200+EXE groups were found to be higher compared to the CONT, Met100, and Met200 groups (P < 0.05). The IL-6 level of the EXE group was determined to be higher than that of the CONT, Met100, and Met200 groups (P < 0.01). It was observed that both exercise and the individual or combined application of metformin resulted in lower blood glucose levels compared to the CONT group. The mean body weight of the EXE group was higher than that of the other groups.
CONCLUSION
The combined application of metformin and exercise has increased osteocalcin and insulin levels compared to metformin application alone.
Topics: Animals; Metformin; Interleukin-6; Osteocalcin; Rats, Wistar; Male; Rats; Physical Conditioning, Animal; Insulin; Hypoglycemic Agents; Blood Glucose; Body Weight
PubMed: 38943302
DOI: 10.4103/njcp.njcp_884_23 -
BMC Cardiovascular Disorders Jun 2024Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been...
BACKGROUND
Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.
METHODS
We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.
RESULTS
Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.
CONCLUSIONS
PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.
Topics: Humans; Heart Failure; Male; Female; Middle Aged; Aged; Predictive Value of Tests; Time Factors; Prognosis; Ventricular Function, Left; Myocardial Perfusion Imaging; Stroke Volume; Risk Factors; Pulmonary Circulation; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Risk Assessment; Ventricular Function, Right; Magnetic Resonance Imaging
PubMed: 38943084
DOI: 10.1186/s12872-024-04003-w -
Physiological Reports Jul 2024The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial... (Review)
Review
The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans-membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss-of-function variant of the gene encoding corin (Cor). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac-derived ANP in these patients, as implied by Feldman et al. Yet, in this mini-review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na and water exertion. Collectively, it seems that beside the classic well-established cardio-renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.
Topics: Humans; Animals; Kidney; Serine Endopeptidases; Atrial Natriuretic Factor; Heart
PubMed: 38942727
DOI: 10.14814/phy2.16105 -
BMJ (Clinical Research Ed.) Jun 2024
Topics: Humans; Off-Label Use; Glucagon-Like Peptide 1; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Europe
PubMed: 38942431
DOI: 10.1136/bmj.q1448