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Translational Andrology and Urology May 2024Penile prosthesis implantation is an effective treatment for erectile dysfunction (ED) with high patient satisfaction and effectiveness. Unfortunately, infections remain... (Review)
Review
Penile prosthesis implantation is an effective treatment for erectile dysfunction (ED) with high patient satisfaction and effectiveness. Unfortunately, infections remain a dreaded complication, often necessitating device removal and imposing a substantial healthcare cost. Biofilms are communities of microorganisms encased in a self-produced polymeric matrix that can attach to penile prostheses. Biofilms have been demonstrated on the majority of explanted prostheses for both infectious and non-infectious revisions and are prevalent even in asymptomatic patients. Biofilms play a role in microbial persistence and exhibit unique antibiotic resistance strategies that can lead to increased infection rates in revision surgery. Biofilms demonstrate physical barriers through the development of an extracellular polymeric substance (EPS) that hinders antibiotic penetrance and the bacteria within biofilms demonstrate reduced metabolic activity that weakens the efficacy of traditional antibiotics. Despite these challenges, new methods are being developed and investigated to prevent and treat biofilms. These treatments include surface modifications, biosurfactants, tissue plasminogen activator (tPA), and nitric oxide (NO) to prevent bacterial adhesion and biofilm formation. Additionally, novel antibiotic treatments are currently under investigation and include antimicrobial peptides (AMPs), bacteriophages, and refillable antibiotic coatings. This article reviews biofilm formation, the challenges that biofilms present to conventional antibiotics, current treatments, and experimental approaches for biofilm prevention and treatment.
PubMed: 38855589
DOI: 10.21037/tau-23-550 -
BioRxiv : the Preprint Server For... Jun 2024Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical...
UNLABELLED
Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in systemic inflammation-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response. Herein, we validated a mouse model of endotoxemia that recapitulates key pathophysiology related to sepsis-induced cognitive dysfunction, including the induction of an acute systemic hyperinflammatory response, blood-brain barrier (BBB) leakage, neurovascular inflammation, and memory impairment after recovery from the systemic inflammatory response. In the acute phase, we identified novel molecular (e.g. upregulation of plasmalemma vesicle associated protein, a driver of endothelial permeability, and the pro-coagulant plasminogen activator inhibitor-1, PAI-1) and functional perturbations (i.e., albumin and small molecule BBB leakage) in the cerebral microvasculature along with neuroinflammation. Remarkably, small molecule BBB permeability, elevated levels of PAI-1, intra/perivascular fibrin/fibrinogen deposition and microglial activation persisted 1 month after recovery from sepsis. We also highlight molecular neuronal alterations of potential clinical relevance following systemic inflammation including changes in neurofilament phosphorylation and decreases in postsynaptic density protein 95 and brain-derived neurotrophic factor suggesting diffuse axonal injury, synapse degeneration and impaired neurotrophism. Our study serves as a standardized model to support future mechanistic studies of sepsis-associated cognitive dysfunction and to identify novel endothelial therapeutic targets for this devastating condition.
SIGNIFICANCE
The limited knowledge of how systemic inflammation contributes to cognitive decline is a major obstacle to the development of novel therapies for dementia and other neurodegenerative diseases. Clinical evidence supports a role for the cerebral microvasculature in sepsis-induced neurocognitive dysfunction, but the investigation of the underlying mechanisms has been limited by the lack of standardized experimental models. Herein, we optimized a mouse model that recapitulates important pathophysiological aspects of systemic inflammation-induced cognitive decline and identified key alterations in the cerebral microvasculature associated with cognitive dysfunction. Our study provides a reliable experimental model for mechanistic studies and therapeutic discovery of the impact of systemic inflammation on cerebral microvascular function and the development and progression of cognitive impairment.
PubMed: 38853992
DOI: 10.1101/2024.05.28.596050 -
Auris, Nasus, Larynx Jun 2024Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by abruptly appearing hearing loss, sometimes accompanied by vertigo. Vascular pathologies (e.g.,... (Review)
Review
Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by abruptly appearing hearing loss, sometimes accompanied by vertigo. Vascular pathologies (e.g., cochlear ischemia, or cochlear infarction) are one of the most likely causes of ISSNHL. This review aims to present current understanding of inner ear anatomy, clinical features of ISSNHL, and its treatment strategies. The labyrinthine artery is the only end artery supplying blood to the inner ear, and it has three branches: the anterior vestibular artery, the main cochlear artery, and the vestibulo-cochlear artery (VCA). Occlusion of the VCA can be caused by a variety of factors. The VCA courses through a narrow bone canal. ISSNHL is usually diagnosed after excluding retrocochlear pathologies of sudden sensorineural hearing loss (SSNHL), such as vestibular schwannoma. Therefore, a head MRI or assessing auditory brainstem responses are recommended for patients with SSNHL. Severe SSNHL patients with high CHADS scores, an index of stroke risk, have a significantly lower rate of vestibular schwannoma than severe SSNHL patients with low CHADS scores, suggesting that severe ISSNHL in individuals at high risk of stroke is caused by vascular impairments. Intralabyrinthine hemorrhage causes SSNHL or vertigo, as in ISSNHL. The diagnosis of intralabyrinthine hemorrhage requires careful interpretation of MRI, and a small percentage of patients diagnosed with ISSNHL may in fact have intralabyrinthine hemorrhage. Many studies have reported an association between ISSNHL and atherosclerosis or cardiovascular risk factors (e.g., diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease), and subsequent risk of stroke in patients with ISSNHL may be elevated compared to controls. Increased hearing level on the healthy ear side, high Framingham risk score, high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, and severe white matter lesions may be poor prognostic factors for patients with ISSNHL. The association between thrombosis-related genes and susceptibility to ISSNHL has been reported in many studies (e.g., coagulation factor 2, coagulation factor 5, plasminogen activator inhibitor-1, platelet-associated genes, a homocysteine metabolism-related enzyme gene, endothelin-1, nitric oxide 3, phosphodiesterase 4D, complement factor H, and protein kinase C-eta). Treatment of ISSNHL with the aim of mitigating the vascular impairment in the inner ear includes systemically administered steroids, intratympanic steroid injections, hyperbaric oxygen therapy, prostaglandin E1, defibrinogenation therapy, and hydrogen inhalation therapy, but there is currently no evidence-based treatment for ISSNHL. Breakthroughs in the unequivocal diagnosis and treatment of ISSNHL due to vascular impairment are crucial to improve quality of life.
PubMed: 38850720
DOI: 10.1016/j.anl.2024.05.009 -
Environmental Epigenetics 2024Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's...
Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study ( = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact -values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, -value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the -values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, -value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.
PubMed: 38846065
DOI: 10.1093/eep/dvae007 -
PloS One 2024Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization...
Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.
Topics: Tissue Plasminogen Activator; Humans; Ischemic Stroke; Recombinant Proteins; Heparin; Thrombolytic Therapy; Fibrinolytic Agents; Blood Coagulation; Erythrocytes; Stroke
PubMed: 38843177
DOI: 10.1371/journal.pone.0302269 -
Journal of Wound Care Jun 2024The aim of this study was to determine the incidence of pressure ulcers (PUs) in patients treated for acute ischaemic stroke (AIS) and to evaluate comorbid/confounding...
OBJECTIVE
The aim of this study was to determine the incidence of pressure ulcers (PUs) in patients treated for acute ischaemic stroke (AIS) and to evaluate comorbid/confounding factors.
METHOD
The study included patients treated for AIS who were divided into three treatment groups: those receiving intravenous tissue plasminogen activator therapy (tPA); patients receiving mechanical thrombectomy (MT); and those receiving both tPA and MT. PUs were classified according to the international classification system and factors that may influence their development were investigated.
RESULTS
A total of 242 patients were included in this study. The incidence of PUs in patients treated for AIS was 7.4%. Most PUs were located on the sacrum (3.7%), followed by the gluteus (3.3%) and trochanter (2.9%). With regards to PU classification: 29% were stage I; 34% were stage II; and the remainder were stage III. Age was not a significant factor in the development of PUs (p=0.172). Patients in the tPA group had a lower PU incidence (2.3%) than patients in the tPA+MT group (15.7%) and MT group (12.1%) (p=0.001). Patients with PUs had a longer period of hospitalisation (18.5±11.92 days) than patients without a PU (8.0±8.52 days) (p=0.000). National Institute of Health Stroke Scale (NIHSS) scores at admission were higher in patients with PUs than in patients without a PU (14.33±4.38 versus 11.08±5.68, respectively; p=0.010). The difference in presence of comorbidities between patients with and without PUs (p=0.922) and between treatment groups (p=0.677) were not statistically significant. The incidence of PUs was higher in patients requiring intensive care, but this difference was not statistically significant (p=0.089).
CONCLUSION
In this study, patients treated for AIS with high NIHSS scores at admission and/or receiving MT were at higher risk for PUs, and so particular attention should be given to these patients in order to prevent PU development.
Topics: Humans; Pressure Ulcer; Male; Female; Ischemic Stroke; Aged; Incidence; Middle Aged; Aged, 80 and over; Tissue Plasminogen Activator; Thrombectomy; Retrospective Studies; Risk Factors; Fibrinolytic Agents
PubMed: 38843015
DOI: 10.12968/jowc.2020.0331 -
Botanical Studies Jun 2024The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past...
BACKGROUND
The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays.
RESULTS
Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium.
CONCLUSIONS
Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.
PubMed: 38842634
DOI: 10.1186/s40529-024-00422-2 -
Frontiers in Endocrinology 2024A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in...
BACKGROUND AND AIMS
A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension.
METHODS
In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol).
RESULTS
Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function.
CONCLUSION
Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.
Topics: Humans; Male; Middle Aged; Female; Hydrocortisone; Dexamethasone; Hypertension; Adult; Thrombosis; von Willebrand Factor; Circadian Rhythm; Aged; Biomarkers
PubMed: 38836224
DOI: 10.3389/fendo.2024.1397062 -
Frontiers in Veterinary Science 2024Chylopericardium is a rare entity in veterinary medicine. In this report we document the development of chylopericardium in two dogs undergoing chronic hemodialysis. An...
Chylopericardium is a rare entity in veterinary medicine. In this report we document the development of chylopericardium in two dogs undergoing chronic hemodialysis. An 11-year-old female spayed Labrador retriever (Case 1) presented with acute coughing and lethargy 2 months following initial dialysis catheter placement and initiation of dialysis therapy for severe azotemia. Echocardiography demonstrated severe pericardial effusion and cardiac tamponade. Pericardial fluid analysis was consistent with chylous effusion. The dog underwent a subtotal pericardiectomy with thoracic duct ligation, and a PleuralPort™ was placed. The patient continued to receive outpatient hemodialysis therapy after pericardiectomy for several months until she died acutely at home. A 4-year-old male neutered Doberman (Case 2) was being treated for 2 months with outpatient hemodialysis for management of chronic kidney disease. On presentation for the 17th hemodialysis treatment, the patient had increased respiratory rate. Echocardiography demonstrated pleural and pericardial effusions, and fluid analysis in both cavities was consistent with chylous effusion. Use of tissue plasminogen activator (TPA), clot removal and replacement of the catheter was attempted; however pleural and pericardial effusion continued. The patient was euthanized after 25 hemodialysis sessions as owners elected not to pursue more procedures. In both cases, the cause of the chylopericardium was suspected to be secondary to catheter-associated thrombosis and/or stenosis based on multiple imaging modalities. Despite use of rivaroxaban and clopidogrel concurrently in each case, the chylous effusion persisted. This case report describes clinical details of a rare complication of long-term indwelling dialysis catheters in two dogs.
PubMed: 38831956
DOI: 10.3389/fvets.2024.1386710 -
BMC Neurology May 2024Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA...
BACKGROUND
Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT.
METHODS
A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3-5) and death within 3 months.
RESULTS
After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31-19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07-3.68; P value = 0.030) in comparison to LNNU.
CONCLUSIONS
High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT.
Topics: Humans; Uric Acid; Female; Male; Neutrophils; Ischemic Stroke; Aged; Middle Aged; Thrombolytic Therapy; Prognosis; Lymphocytes; Retrospective Studies; Aged, 80 and over; Administration, Intravenous; Fibrinolytic Agents
PubMed: 38822243
DOI: 10.1186/s12883-024-03628-w