-
Urology Journal May 2024Platelet-rich plasma (PRP) is enriched with active biological components which showed proliferative and cytoprotective properties in healing different injuries in...
Application of Autologous Platelet-rich Plasma Exerts Cryoprotective Effects on Biological Characteristics of Human Oligoasthenoteratospermia Samples after Freezing and Thawing Procedures.
OBJECTIVE
Platelet-rich plasma (PRP) is enriched with active biological components which showed proliferative and cytoprotective properties in healing different injuries in medicinal fields. This study was designed to assess cryoprotective effects of autologous PRP on quality of oligoasthenoteratospermia (OAT) samples during freezing and thawing procedure.
MATERIALS AND METHODS
The present study is an experimental research. Twenty OAT semen samples were obtained from individuals and prepared by discontinuous density - gradients technique. Control group is sperm samples after DGC. After the procedure, the specimen divided into four groups. Freeze group which has no additive and other three groups were cryopreserved with different concentrations of PRP (1×105/µL, 0.5×105/µL and 0.25×105/µL). Autologous PRP was provided by each participant. After thawing, sperm parameters, DNA fragmentation by sperm chromatin dispersion test (SCD), protamine deficiency by (Chromomycin A3) CMA3 staining, acrosome integrity and malondialdehyde (MDA) level were evaluated.
RESULTS
Cryopreservation resulted in significant decreased in all factors compared to the control group. There were no significant changes on sperm count, morphology, non-progressive motility and acrosome reaction by adding PRP as cryoprotectant in comparison with freeze group. PRP at all three concentrations showed significant increase in progressive motility (3.05±2.01 vs. 14.05±4.13, 12.35±4.90 and 12.15±9.65, P<0.001) and viability (36.85±10.25 vs. 47.85±5.86, 51.30±5.54 and 50.05±5.67, P<0.001) compared to the sperm samples without PRP. The percentage of immotile sperms decreased at all PRP concentrations compared to the freeze group. Moreover, PRP at 1×105/µL concentration showed cryoprotective effects on DNA fragmentation, protamine deficiency and MDA level compared to the other three concenterations.
CONCLUSION
Cryopreservation and thawing procedures may exert adverse effects on biological factors of sperm samples. Therefore, adding PRP as cryoprotectant at all three concentrations especially 1×105/µL can be promising strategy to reduce adverse effects of cryopreservation on OAT samples.
PubMed: 38733230
DOI: 10.22037/uj.v21i.8013 -
Molecular Pain 2024Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and...
Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.
Topics: Animals; Hyaluronic Acid; Male; Female; Rats; Rats, Sprague-Dawley; Administration, Cutaneous; Protamines; Molecular Weight; Serotonin; Administration, Topical
PubMed: 38728068
DOI: 10.1177/17448069241254455 -
International Journal of Molecular... Apr 2024Semen cryopreservation has played an important role in medically assisted reproduction for decades. In addition to preserving male fertility, it is sometimes used for...
Semen cryopreservation has played an important role in medically assisted reproduction for decades. In addition to preserving male fertility, it is sometimes used for overcoming logistical issues. Despite its proven clinical usability and safety, there is a lack of knowledge of how it affects spermatozoa at the molecular level, especially in terms of non-coding RNAs. Therefore, we conducted this study, where we compared slow freezing and vitrification of good- and poor-quality human semen samples by analyzing conventional sperm quality parameters, performing functional tests and analyzing the expression of miRNAs. The results revealed that cryopreservation of normozoospermic samples does not alter the maturity of spermatozoa (protamine staining, hyaluronan binding), although cryopreservation can increase sperm DNA fragmentation and lower motility. On a molecular level, we revealed that in both types of cryopreservation, miRNAs from spermatozoa are significantly overexpressed compared to those in the native semen of normozoospermic patients, but in oligozoospermic samples, this effect is observed only after vitrification. Moreover, we show that expression of selected miRNAs is mostly overexpressed in native oligozoospermic samples compared to normozoospermic samples. Conversely, when vitrified normozoospermic and oligozoospermic samples were compared, we determined that only miR-99b-5p was significantly overexpressed in oligozoospermic sperm samples, and when comparing slow freezing, only miR-15b-5p and miR-34b-3p were significantly under-expressed in oligozoospermic sperm samples. Therefore, our results imply that cryopreservation of normozoospermic sperm samples can modulate miRNA expression profiles in spermatozoa to become comparable to those in oligozoospermic samples.
Topics: Humans; MicroRNAs; Male; Cryopreservation; Vitrification; Semen Analysis; Semen Preservation; Semen; Spermatozoa; Sperm Motility; Freezing; Adult; DNA Fragmentation
PubMed: 38673743
DOI: 10.3390/ijms25084157 -
Toxics Apr 2024Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male...
BACKGROUND
Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders.
METHODS
Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected.
RESULTS
The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue.
CONCLUSION
These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.
PubMed: 38668519
DOI: 10.3390/toxics12040296 -
International Journal of Endocrinology... Oct 2023Type 1 diabetes mellitus (T1DM) is a prevalent chronic disease among children and adolescents, necessitating effective self-monitoring of blood glucose (SMBG) levels....
BACKGROUND
Type 1 diabetes mellitus (T1DM) is a prevalent chronic disease among children and adolescents, necessitating effective self-monitoring of blood glucose (SMBG) levels. Understanding the determinants and factors influencing SMBG behavior is crucial for optimizing diabetes management in this population.
OBJECTIVES
This study aimed to investigate the frequency of SMBG and identify the determinants influencing factors in children and adolescents with T1DM.
METHODS
This cross-sectional study was conducted in Tehran, Iran, and included 275 participants selected through simple random sampling from the Gabric Diabetes Education Association. The inclusion criteria comprised children and adolescents aged 3 - 18 years diagnosed with T1DM for at least 6 months who were using analog or neutral protamine Hagedorn (NPH) and regular insulin subcutaneously. Patients using insulin pumps were excluded. Data collection involved an online questionnaire covering demographic information (e.g., age, gender, educational status, and parental occupations) as well as clinical information (number of hypoglycemic episodes, hemoglobin A1C (HbA1C) levels, diabetes duration, insulin regimen, diabetes complications, glucose monitoring practices, hospitalizations, and behavioral characteristics). Statistical analyses, including descriptive statistics, correlation tests, and Poisson regressions, were performed using SPSS software (version 21). A significance level of P-value < 0.05 was considered statistically significant.
RESULTS
The participants had a mean age of 10.00 ± 3.77 years, with 54.2% being males. Most of the participants (87.3%) were schoolchildren, and the mean age of diagnosis was 6.56 ± 3.73 years, with a mean duration of 44.72 ± 36.32 months. Anthropometric investigations revealed mean height, weight, and body mass index (BMI) values of 136.69 ± 21.11 cm, 37.45 ± 15.51 kg, and 18.31 ± 3.55 kg/m, respectively. The majority of participants (93.5%) used insulin pens, and the mean daily insulin dosage was 35.34 ± 22.20 IU. Parents reported consistent glucose level monitoring in 64.7% of cases. The mean HbA1c level was 7.91 ± 1.58%. Factors such as the price and availability of glucometer strips influenced glucose level monitoring. In univariate analysis, only age and HbA1C levels showed a negative correlation; however, parents' consistent checking showed a positive correlation with the frequency of daily, weekly, or monthly glucose checking.
CONCLUSIONS
This study underscores the significance of SMBG in children and adolescents with T1DM. The findings emphasize the critical role of price and availability of glucometers and strips in achieving standard care for T1DM patients.
PubMed: 38666044
DOI: 10.5812/ijem-138377 -
Journal of Diabetes May 2024The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and... (Comparative Study)
Comparative Study
INTRODUCTION
The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH).
METHODS
This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life.
RESULTS
Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m at conception and 26.32 kg/m at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH.
CONCLUSIONS
Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.
Topics: Humans; Female; Pregnancy; Diabetes Mellitus, Type 1; Adult; Insulin; Insulin Infusion Systems; Prospective Studies; Hypoglycemic Agents; Pregnancy in Diabetics; Injections, Subcutaneous; Glycated Hemoglobin; Pregnancy Outcome; Infusions, Subcutaneous; Blood Glucose; Quality of Life; Glycemic Control
PubMed: 38664886
DOI: 10.1111/1753-0407.13558 -
Clinical and Applied... 2024Andexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is...
INTRODUCTION
Andexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO for heparins of bovine, ovine, and porcine origin.
MATERIALS AND METHODS
The neutralization effect of PrSO at 25 µg/ml and AA at 100 µg/ml was studied on an approximate surgical/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 µg/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from -10-0.62 µg/ml.
RESULTS
In the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400-450 seconds) compared to saline (130-150 seconds). Both AA and PrSO almost fully neutralized the anti-coagulant effects of heparins (140-160 seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects.
CONCLUSION
Andexanet alfa at 100 µg/ml effectively neutralizes the therapeutic and surgical/interventional concentrations of heparins in settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.
Topics: Recombinant Proteins; Factor Xa; Cattle; Sheep; Swine; Animals; Anticoagulants; Heparin; Protamines; Heparin Antagonists; Blood Coagulation; Thrombin Time
PubMed: 38656136
DOI: 10.1177/10760296241247558 -
Annals of Internal Medicine May 2024In the United States, costs of antidiabetes medications exceed $327 billion. (Review)
Review
Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.
BACKGROUND
In the United States, costs of antidiabetes medications exceed $327 billion.
PURPOSE
To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes.
DATA SOURCES
Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English.
STUDY SELECTION
Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer.
DATA EXTRACTION
Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative.
DATA SYNTHESIS
Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE).
LIMITATIONS
Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established.
CONCLUSION
Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022382315).
Topics: Diabetes Mellitus, Type 2; Humans; Cost-Benefit Analysis; Hypoglycemic Agents; Quality-Adjusted Life Years; United States; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38639547
DOI: 10.7326/M23-1492 -
Journal of Cardiothoracic Surgery Apr 2024Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and...
BACKGROUND
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin.
CASE PRESENTATION
We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia.
CONCLUSION
The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.
Topics: Male; Humans; Child; Heparin; Fondaparinux; Drug Hypersensitivity Syndrome; Anticoagulants; Hirudins; Eosinophilia; Peptide Fragments; Anesthetics; Recombinant Proteins
PubMed: 38632589
DOI: 10.1186/s13019-024-02722-x -
Nucleus (Austin, Tex.) Dec 2024Species' continuity depends on gametogenesis to produce the only cell types that can transmit genetic information across generations. Spermiogenesis, which encompasses... (Review)
Review
Species' continuity depends on gametogenesis to produce the only cell types that can transmit genetic information across generations. Spermiogenesis, which encompasses post-meiotic, haploid stages of male gametogenesis, is a process that leads to the formation of sperm cells well-known for their motility. Spermiogenesis faces three major challenges. First, after two rounds of meiotic divisions, the genome lacks repair templates (no sister chromatids, no homologous chromosomes), making it incredibly vulnerable to any genomic insults over an extended time (typically days-weeks). Second, the sperm genome becomes transcriptionally silent, making it difficult to respond to new perturbations as spermiogenesis progresses. Third, the histone-to-protamine transition, which is essential to package the sperm genome, counterintuitively involves DNA break formation. How spermiogenesis handles these challenges remains poorly understood. In this review, we discuss each challenge and their intersection with the biology of protamines. Finally, we discuss the implication of protamines in the process of evolution.
Topics: Male; Humans; Semen; Spermatogenesis; Histones; Spermatozoa; Protamines
PubMed: 38594652
DOI: 10.1080/19491034.2024.2339220