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Scientific Reports Jun 2024Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to...
Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to examine the visfatin effect on the secretion of steroid (P, E) and prostaglandin (PGE, PGF), the mRNA and protein abundance of steroidogenic markers (STAR, CYP11A1, HSD3B, CYP19A1), prostaglandin receptors (PTGER2, PTGFR), insulin receptor (INSR), and activity of kinases (MAPK/ERK1/2, AKT, AMPK) in the porcine corpus luteum. We noted that the visfatin effect strongly depends on the phase of the estrous cycle: on days 2-3 and 14-16 it reduced P, while on days 10-12 it stimulated P. Visfatin increased secretion of E on days 2-3, PGE on days 2-3 and 10-12, reduced PGF release on days 14-16, as well as stimulated the expression of steroidogenic markers on days 10-12 of the estrous cycle. Moreover, visfatin elevated PTGER mRNA expression and decreased its protein level, while we noted the opposite changes for PTGFR. Additionally, visfatin activated ERK1/2, AKT, and AMPK, while reduced INSR phosphorylation. Interestingly, after inhibition of INSR and signalling pathways visfatin action was abolished. These findings suggest a regulatory role of visfatin in the porcine corpus luteum.
Topics: Animals; Corpus Luteum; Female; Swine; Nicotinamide Phosphoribosyltransferase; Estrous Cycle; Receptor, Insulin; Progesterone; Receptors, Prostaglandin; Dinoprost
PubMed: 38926439
DOI: 10.1038/s41598-024-65102-4 -
Biological & Pharmaceutical Bulletin 2024We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel...
We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.
Topics: Animals; Arginine; Hydrogels; Mice, Hairless; Skin Absorption; Administration, Cutaneous; Skin; Indomethacin; Decanoic Acids; Hydrocortisone; Mice; Rheology; Permeability; Male
PubMed: 38925923
DOI: 10.1248/bpb.b24-00078 -
Ceska a Slovenska Oftalmologie :... 2024The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to...
OBJECTIVE
The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment.
MATERIAL AND METHODS
This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated.
RESULTS
At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%).
CONCLUSION
Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).
Topics: Humans; Macular Edema; Male; Female; Diabetic Retinopathy; Dexamethasone; Retrospective Studies; Middle Aged; Aged; Intravitreal Injections; Drug Implants; Visual Acuity; Glucocorticoids; Tomography, Optical Coherence
PubMed: 38925895
DOI: 10.31348/2024/29 -
Transplant International : Official... 2024In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and... (Observational Study)
Observational Study
In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week and correlated with eGFR (r = 0.273; = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r = 0.54, = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.
Topics: Humans; Kidney Transplantation; Male; Female; Middle Aged; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Glomerular Filtration Rate; Longitudinal Studies; Adult; Aldosterone; Aged; Renin; Water-Electrolyte Imbalance; Body Composition; Blood Glucose; Transplant Recipients
PubMed: 38915756
DOI: 10.3389/ti.2024.12879 -
Frontiers in Immunology 2024With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in...
With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.
Topics: Humans; Female; Aged; Adrenal Insufficiency; Immune Checkpoint Inhibitors; Addison Disease; Hydrocortisone
PubMed: 38915406
DOI: 10.3389/fimmu.2024.1371527 -
Journal of Hematology & Oncology Jun 2024It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of...
It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.
Topics: Humans; Multiple Myeloma; Aged; Prospective Studies; Male; Female; Aged, 80 and over; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Frailty; Lenalidomide; Bortezomib; Precision Medicine; Frail Elderly; Geriatric Assessment; Antibodies, Monoclonal
PubMed: 38915117
DOI: 10.1186/s13045-024-01569-y -
Scientific Reports Jun 2024Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro... (Meta-Analysis)
Meta-Analysis Comparative Study
Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its' clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ: 0.11, OHSS χ: 0.26), moderate (Clinical Pregnancy: χ: 7.02, Live birth χ: 10.95, Biochemical pregnancy: χ: 6.60, Miscarriage: χ: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.
Topics: Humans; Female; Sperm Injections, Intracytoplasmic; Pregnancy; Network Meta-Analysis; Fertilization in Vitro; Luteal Phase; Pregnancy Rate; Progesterone; Live Birth; Bayes Theorem; Ovulation Induction; Randomized Controlled Trials as Topic; Ovarian Hyperstimulation Syndrome; Abortion, Spontaneous
PubMed: 38914570
DOI: 10.1038/s41598-024-64804-z -
BMJ Open Jun 2024Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and...
INTRODUCTION
Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.
METHODS AND ANALYSIS
This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.
ETHICS AND DISSEMINATION
This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.
TRIAL REGISTRATION NUMBER
jRCTs041210027.
Topics: Humans; Histiocytosis, Langerhans-Cell; Child; Adolescent; Japan; Adult; Dexamethasone; Young Adult; Zoledronic Acid; Male; Female; Clinical Trials, Phase II as Topic; Child, Preschool; Bone Density Conservation Agents
PubMed: 38910000
DOI: 10.1136/bmjopen-2024-084159 -
Nature Communications Jun 2024Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to...
Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.
Topics: Humans; Female; Pregnancy; China; Maternal Exposure; Adult; Premature Birth; Pregnancy Trimester, First; Prospective Studies; Pregnancy Outcome; Dydrogesterone; Progesterone; Birth Cohort; Infant, Newborn; Abortion, Spontaneous; Stillbirth; Infant, Low Birth Weight; Longitudinal Studies; Incidence; Young Adult
PubMed: 38906856
DOI: 10.1038/s41467-024-49623-0 -
Medicine Jun 2024Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH...
INTRODUCTION
Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection.
PATIENT CONCERNS
We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated.
DIAGNOSIS
The patient fulfilled diagnostic criteria for HLH.
INTERVENTIONS
Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed.
OUTCOMES
After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized.
LESSIONS
The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Child, Preschool; Otitis Media; Acute Disease; Dexamethasone; Cyclosporine; Etoposide; Immunoglobulins, Intravenous
PubMed: 38905364
DOI: 10.1097/MD.0000000000038616