Search Results (119)

Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. Twenty-one male rats were divided into three groups: control (K), benzodiazepine-treated (B), and alcohol-treated (A). After two weeks of substance administration, hypothermia was induced and multiple organ samples were analyzed. Histologically, renal tissue showed hydropic and vacuolar degeneration, congestion, and acute tubular injury across all groups, with no significant differences in E-cadherin expression. Lung samples revealed congestion, emphysema, and hemorrhage, with more pronounced vascular congestion in the alcohol and benzodiazepine groups. Cardiac tissue exhibited vacuolar degeneration and protein denaturation, particularly in substance-exposed animals. The spleen showed preserved architecture but increased erythrocyte infiltration and significantly elevated myeloperoxidase (MPO)-positive granulocytes in the intoxicated groups. Liver samples demonstrated congestion, focal necrosis, and subcapsular hemorrhage, especially in the alcohol group. Immunohistochemical analysis revealed statistically significant differences in MPO expression in both lung and spleen tissues, with the highest levels observed in the benzodiazepine group. Similarly, CK7 and CK20 expression in the gastroesophageal junction was significantly elevated in both alcohol- and benzodiazepine-treated animals compared to the controls. In contrast, E-cadherin expression in the kidney did not differ significantly among the groups. These findings suggest that specific histological and immunohistochemical patterns, particularly involving pulmonary, cardiac, hepatic, and splenic tissues, may help differentiate primary hypothermia from substance-related secondary hypothermia. The study underscores the value of integrating toxicological, histological, and molecular analyses to enhance the forensic assessment of hypothermia-related fatalities. Future research should aim to validate these markers in human autopsy series and explore additional molecular indicators to refine diagnostic accuracy in forensic pathology. Full article

Pregnancy rhinitis (PR) is a transient, non-infectious nasal condition affecting a significant number of pregnant women, yet often remains underdiagnosed or misclassified. It can substantially impact maternal quality of life, sleep, and even fetal oxygenation. This narrative review explores the current understanding of PR, including hormonal and vascular mechanisms, clinical criteria, and therapeutic approaches considered safe during pregnancy. Despite increasing recognition, the differentiation between PR and other rhinitis forms remains challenging. Limited therapeutic options and the absence of standard diagnostic guidelines further complicate management. Evidence supports a multifactorial etiology involving estrogen, progesterone, and placental growth factors. Non-pharmacologic strategies are first-line, while pharmacological interventions are cautiously employed. PR is a distinct and clinically relevant condition requiring increased awareness among ENT and obstetric professionals. Future research should focus on standardized diagnostic criteria and evidence-based treatment protocols to improve maternal–fetal outcomes. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article

Umbilical cord mesenchymal stem cells (UCMSCs)-derived small extracellular vehicles (sEVs) are reported to offer therapeutic effects in regenerative medicine, but they lack safety and biodistribution profiles to support smooth translation at the clinical stage and regulatory requirements. Our study aimed to determine the safety and biodistribution profile in a healthy animal model before application in the metabolic syndrome model. Method: Healthy male Sprague Dawley (SD) rats were given an intravenous (IV) injection of normal saline (control group) or pooled fetal UCMSCs-derived sEVs (treated group) every three weeks for 90 days. Morbidity and mortality observation (daily), physical measurements (weekly), selected serum biochemistry (every three weeks), and hematology (every three weeks) were performed for 90 days. Acute toxicity (on day 14) and sub-chronic toxicity (on day 90) were assessed for gross necropsy, relative organ weight, and histopathological assessment of lungs, liver, spleen, kidney, and lymph nodes. Separately, a biodistribution study was conducted with the sEVs preparations labeled with PKH26 fluorescent dye, given intravenously to the rats. The organs were harvested 24 h post-injection. There were no drastic changes in either group’s morbidity or mortality, physical, hematological, and biochemistry evaluation. The histopathological assessment concluded moderate (focal) inflammation in the treated group’s kidneys and signs of recovery from the inflammation and vascular congestion in the liver. A biodistribution study revealed a higher accumulation of sEVs in the spleen. Multiple IV injections of the pooled fetal UCMSCs-derived sEVs in healthy male SD rats were deemed safe. The sEVs were abundantly distributed in the spleen 24 h post-injection. Full article

Hemodynamic assessment is critical in emergency and critical care for preventing, diagnosing, and managing shock states that significantly affect patient outcomes. Point-of-care ultrasound (POCUS) has become an invaluable, non-invasive, real-time, and reproducible tool for bedside decision-making. Advancements such as Doppler imaging, advanced critical care ultrasonography, and transesophageal echocardiography (TEE) have expanded its utility, enabling rapid and repeatable evaluations, especially in complex mixed shock presentations. This review explores the role of POCUS in hemodynamic monitoring, emphasizing its ability to assess cardiac output, filling pressures, and vascular congestion, facilitating shock classification and guiding fluid management. We highlight an extensive array of POCUS techniques for evaluating right and left cardiac function and review existing literature on their advantages, limitations, and appropriate clinical applications. Beyond assessing volume status, this review discusses the role of POCUS in predicting fluid responsiveness and supporting more individualized, precise management strategies. Ultimately, while POCUS is a powerful tool for rapid, comprehensive hemodynamic assessment in acute settings, its limitations must be acknowledged and thoughtfully integrated into clinical decision-making. Full article

Heart failure (HF) remains a major global health challenge, driven by multifactorial pathophysiological processes, such as systemic congestion, endothelial dysfunction, and inflammation. While natriuretic peptides are well-established biomarkers for diagnosing and monitoring HF, they do not fully capture the complexity of vascular involvement. CD146, also known as melanoma cell adhesion molecule (MCAM), is a transmembrane glycoprotein primarily expressed on endothelial cells and involved in cell adhesion, vascular permeability, and angiogenesis. Its soluble form (sCD146), released in response to multiple pathophysiological stimuli, including venous and arterial endothelial stretch, oxidative stress, and inflammatory cytokine activation, has emerged as a promising biomarker reflecting both hemodynamic congestion and systemic endothelial stress. This review synthesizes current knowledge on the structure, regulation, and release mechanisms of CD146 and explores its clinical utility in HF. Elevated sCD146 levels have been associated with echocardiographic and radiological indicators of congestion, as well as with adverse outcomes. While promising, its application is limited by variability, lack of standardization, and confounding elevations in non-cardiac conditions, including malignancy. Full article

This study aimed to investigate the effect of Artemisia absinthium extract on testicular dysfunction in rats and explain the involvement of the androgen receptor signaling pathway as a biomarker in maintaining fertility during sodium fluoride (NaF) treatment. Thirty-two male rats were divided equally into four groups and received treatment for 60 days. The control group (I) received normal saline; group II received Artemisia extract at 100 mg/kg b.w.; group III received NaF at 12 mg/kg b.w. orally; and group IV received NaF (12 mg/kg b.w.) and Artemisia extract (100 mg/kg b.w.). The testis weights and the lipid peroxidation, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were estimated. The genital organs were prepared and immunoreacted with a receptor. Histomorphometric analyses were performed to obtain the diameter of the seminiferous tubules and the height of the germinal epithelia in the testes. The results showed that exposure to NaF caused a significant increase in testis weight and malondialdehyde (MDA) and a decrease in serum LH, FSH, and testosterone concentrations compared to the control group, while extract administration induced an increase in the levels of these hormones in group IV. Testicular histological and histomorphometric changes were observed in group III: degenerative seminiferous tubules with vascular congestion, disorganization of the germinal layer, and decreased seminiferous tubule diameter and germinal epithelium height. The expression of androgen receptors in the testes of the NaF-treated rats was significantly reduced. In contrast, these testicular histological changes were ameliorated in rats treated with the extract. The results allow us to conclude that the administration of Artemisia absinthium confers positive effects on male reproductive function by inhibiting fluoride, maybe via ameliorative testicular function. Full article

Kidney disorders significantly contribute to morbidity and mortality in sickle cell disease (SCD). Acute kidney injury (AKI), a major risk factor for chronic kidney disease (CKD), often arises from intravascular hemolysis, where plasma cell-free heme drives AKI through inflammatory and oxidative stress mechanisms. Hydroxyurea (HU), a well-established SCD-modifying therapy, improves clinical outcomes, but its effects on systemic heme and inflammatory mediators of kidney injury remain underexplored. This study evaluated HU’s impact on plasma heme, pro-inflammatory mediators, kidney injury, and renal histopathology in a sickle cell mouse model. Townes humanized sickle cell mice (HbSS) and non-sickle (HbAA) controls were treated with HU or vehicle for two weeks. HU significantly reduced total plasma heme, lactate dehydrogenase, and pro-inflammatory cytokines (CXCL10, VEGF-A, IFN-γ) in HbSS mice. HU reduced renal injury biomarkers (cystatin C, NGAL) and improved renal histopathology, evidenced by reduced vascular congestion, glomerulosclerosis, and tubular damage. Interestingly, HU did not alter the levels of kidney repair biomarkers (clusterin and EGF). These findings suggest that HU mitigates kidney injury by reducing the deleterious effects of circulating heme and inflammation, supporting its potential to slow or prevent progressive kidney injury in SCD. Full article

Plant extracts with antioxidant activities have shown nephroprotection against IR injury. Jatropha dioica (Jd) possesses antioxidant activity. Our aim was to evaluate the effects of a hydroalcoholic Jd extract against IR injury in Wistar rats. Rats were divided into groups (n = 6): sham (SH); no toxicity (JdTox; 300 mg/kg/day of extract for 7 days); IR (on day 7 [I: 45 min/R: 24 h]); and Jd+IR (same treatment as JdTox; same surgical procedure as IR). AST and LDH were significantly lower in the JdTox. IR exhibited significantly higher CrS, BUN, and MDA compared with SH; Jd+IR showed reductions in these markers. GSH and SOD levels were significantly lower in IR compared with SH; an increase in these markers was observed in the Jd+IR. Histologically, IR showed significant increases in medullary tubular necrosis, medullary protein casts, and medullary vascular congestion compared with SH and JdTox. In Jd+IR, a significant decrease was observed only in medullary tubular necrosis. Therefore, the evaluated hydroalcoholic Jd extract dose showed no nephrotoxicity and hepatotoxicity. Jd extract pretreatment attenuated IR-induced renal injury, as evidenced by the improved serum markers of renal damage and oxidative stress. Full article

The renal resistive index (RRI), a Doppler ultrasound-derived parameter measuring renal vascular resistance, has emerged as a promising non-invasive tool to evaluate renal hemodynamics in critically ill patients, particularly those with acute respiratory distress syndrome (ARDS) and heart failure (HF). This narrative review examines the current evidence for RRI measurement in these conditions, exploring its physiological bases, methodology, clinical applications, and limitations. In ARDS, RRI reflects the complex interactions between positive pressure ventilation, hypoxemia, and systemic inflammation, showing a role in predicting acute kidney injury and monitoring response to interventions. In HF, RRI is able to assess venous congestion and cardiorenal interactions and can also serve as a prognostic indicator. Many studies have shown RRI’s superiority or complementarity to traditional biomarkers in predicting renal dysfunction, although its interpretation requires consideration of multiple patient-related factors. Key challenges include operator dependency, lack of standardization, and complex interpretation in multi-organ dysfunction. Future research should focus on measurement standardization, development of automated techniques, investigation of novel applications like intraparenchymal renal resistive index variation, and validation of RRI-guided management strategies. Despite its limitations, RRI represents a valuable tool that offers bedside and real-time insights into renal hemodynamics and potential guidance for therapeutic interventions. Further research is needed to fully clarify its clinical potential and address current limitations, particularly in critical care settings involving multiple organ dysfunction. Full article

Background/Objectives: Diabetic cardiomyopathy is a distinct myocardial dysfunction characterized by structural and functional changes in the heart that occur in diabetic patients independently of coronary artery disease or hypertension. It is closely associated with oxidative stress, inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, and contributes to progressive cardiac damage. This study aimed to evaluate the cardioprotective effects of dapagliflozin (DAPA) and trimetazidine (TMZ) in a rat model of doxorubicin-induced cardiomyopathy with streptozotocin-induced diabetes, focusing on their potential mechanisms related to ER stress. Methods: A total of 48 Sprague Dawley rats aged 6–8 weeks were randomly distributed equally into six cages. The diabetes model was induced by intraperitoneal administration of streptozotocin (STZ) and rats with blood glucose levels above 250 mg/dL were considered diabetic. For those rats with diabetes, cardiotoxicity was induced by intraperitoneal injection of 5 mg/kg/week doxorubicin (DOXO) for 4 weeks. After a cumulative dose of 20 mg/kg doxorubicin, a week break was given, followed by the administration of TMZ (10 mg/kg) and/or DAPA (10 mg/kg) to the treatment groups. Results: STZ administration caused diabetes and significant degeneration in cardiomyocytes. With the addition of DOXO (STZ + DOXO), cardiomyocyte degeneration became more severe. When the study groups were histopathologically evaluated based on parameters of degenerative cardiomyocytes, vascular congestion, and edema, it was shown that both TMZ and DAPA, whether applied alone or in combination, reduced damage in heart tissue. Both TMZ and DAPA reduced cardiomyocyte damage, and their combination provided the lowest level of damage through the reduced ER stress pathway by reducing GRP 78 and CHOP positivity. Conclusions: TMZ and DAPA reduce ER stress and have protective effects against diabetic-induced cardiotoxicity. Combination therapy or TMZ was found to be more effective than DAPA in alleviating ER stress. Combination therapy appears to carry potential effects for reducing cardiac cell damage in individuals with diabetes. Full article

Background/Objectives: We aim to quantify the effect of sex upon the presentation of acute lower limb ischemia (ALI) and the outcomes after surgical thromboembolectomy with a Fogarty catheter. Methods: This was a monocentric retrospective observational study of ALI treated by a Fogarty catheter. Demographics, comorbidities, and clinical characteristics were analyzed. The logistic regressions were used to estimate mortality and secondary outcomes. Results: Over 8 years, 193 patients (79 males and 114 females) underwent Fogarty catheter thromboembolectomy to treat acute lower limb ischemia. Females were older (74.5 for females vs. 82.5 for males) and more affected by congestive heart failure (27% vs. 8%; p = 0.001) and atrial fibrillation (68% vs. 37%; p = <0.001) than the male counterparts. Regarding etiology (p < 0.001), a cardiac embolism (males: 35%; females: 67%) and aortic thrombosis (males: 1%; females: 8%) were more associated with the female gender in the development of acute lower limb ischemia, while vascular bypass/endograft failure (males: 20%; females: 7%) and iatrogenic complications (males: 13%; females: 1%) were more associated with the male gender. After 30 days from surgery, 19% of men and 32% of women had died. Males had higher rates of loss of vascular patency (males: 25%; females: 9%; p = 0.002) and vascular reintervention (males: 20%; females: 8%; p = 0.012). After 90 days from surgery, 23% of men and 41% of women had died. If women had higher mortality (males: 23%; females: 41%; p = 0.008), men had higher rates of loss of vascular patency (males: 27%; females: 12%; p = 0.011) and vascular reintervention (males: 23%; females: 9%; p = 0.007). Conclusions: Older females with atrial fibrillation and/or chronic heart failure are at high risk for ALI. Regarding the thromboembolectomy with a Fogarty catheter, male sex appears to be a risk factor (OR: 2.2, CI: 1.08–4.56) for loss of primary patency, major amputation, and new vascular surgery. A further prospective analysis is warranted to understand the impact of sex in the presentation of acute lower limb ischemia (ALI) and the outcome after surgical thromboembolectomy. Full article

Background and Objectives: Ischemia–reperfusion (I/R) injury can affect multiple distant organs following I/R in the lower extremities. BPC-157’s anti-inflammatory and free radical-neutralizing properties suggest its potential in mitigating ischemia–reperfusion damage. This study evaluates the protective effects of BPC-157 on remote organ damage, including the kidneys, liver, and lungs, in a rat model of skeletal muscle I/R injury. Materials and Methods: A total of 24 male Wistar albino rats were randomly divided into four groups: sham (S), BPC-157(B), lower extremity I/R(IR) and lower extremity I/R+BPC-157(I/RB). Some 45 min of ischemia of lower extremity was followed by 2 h of reperfusion of limbs. BPC-157 was applied to groups B and I/RB at the beginning of the procedure. After 2 h of reperfusion, liver, kidney and lung tissues were harvested for biochemical and histopathological analyses. Results: In the histopathological examination, vascular and glomerular vacuolization, tubular dilation, hyaline casts, and tubular cell shedding in renal tissue were significantly lower in the I/RB group compared to other groups. Lung tissue showed reduced interstitial edema, alveolar congestion, and total damage scores in the I/RB group. Similarly, in liver tissue, sinusoidal dilation, necrotic cells, and mononuclear cell infiltration were significantly lower in the I/RB group. Additionally, the evaluation of TAS, TOS, OSI, and PON-1 revealed a statistically significant increase in antioxidant activity in the liver, lung, and kidney tissues of the I/RB group. Conclusions: The findings of this study demonstrate that BPC-157 exerts a significant protective effect against distant organ damage in the liver, kidneys, and lungs following lower extremity ischemia–reperfusion injury in rats. Full article

Background and Objectives: The aim was to evaluate nerve healing using immunohistochemical, histological, and functional techniques and to compare the effects of two different therapeutic ozone application methods by perineural and intraperitoneal ozone treatment in rats with a crush injury model of sciatic nerve. Materials and Methods: Forty male Sprague Dawley rats were divided into four subgroups of ten rats each: (1) Control group: The left sciatic nerve incised and closed without crush injury, no treatment; (2) Paralyzed group: Crush injury to the left sciatic nerve, no treatment; (3) Perineural ozone group: Crush injury to the left sciatic nerve, treated with perineural ozone therapy; (4) Intraperitoneal ozone group: Crush injury to the left sciatic nerve, treated with intraperitoneal ozone therapy. The treatments were administered for a 14-day period. Hematoxylin and eosin (H&E) and toluidine blue staining were used for histological examination; TUNEL staining was used for immunohistochemical examination. Pinch test and rotarod performance assessment were utilized for functional evaluation. Results: The pinch test scores showed significant improvement in perineural and intraperitoneal ozone treatment groups after treatment (p < 0.001 and p = 0.003, respectively). The scores of myelin degeneration, vascular congestion, vascular wall thickness, inflammation, and toluidine blue and TUNEL staining were significantly lower in both ozone treatment groups compared to the paralyzed group (p < 0.001). Vascular wall thickness scores were significantly higher in the perineural ozone group compared to the control and intraperitoneal ozone groups (p = 0.004 and p = 0.013, respectively). The Schwann cell proliferation scores were significantly higher in the perineural ozone group compared to the control group and intraperitoneal ozone groups (p < 0.001). Conclusions: Both applications of ozone therapy accelerated the healing of nerve regeneration, reduced inflammation and apoptosis based on histopathological results, and enhanced nerve function in rats with sciatic nerve injury. Perineural ozone therapy has been demonstrated to be an efficacious alternative to systemic ozone treatments in the management of sciatic nerve injury. Further studies are needed to determine optimal ozone dosage and administration protocols for the treatment of nerve injury. Full article

Background and Objectives: Vein of Galen aneurysmal malformations (VGAMs) represent the most common vascular malformations of the brain at the pediatric age. Comprehension of its angioarchitecture and clinical features may influence their treatment options and functional outcomes. The aim of this review is to give an update of the anatomical and technical aspects of the management of VGAMs after endovascular treatment. Materials and Methods: We conducted a systematic review of original articles published between 1 January 2014 and 1 February 2024 in Pubmed, Web of Science (WOS), and Scopus databases following PRISMA guidelines. Variables such as age, sex, angioarchitecture of the malformation, clinical presentation, embolization technique, rate of occlusion, post-procedural complications, follow-up time, and mortality were collected. Random-effect meta-analysis of proportions was performed. Results: Fifteen studies on a total of 400 patients with VGAMs were collected. A total of 65.1% was male. The age at diagnosis was 12% prenatal, 35.5% neonates, 34.1% infants, 15.1% children, and 3.3% adults. Clinical presentation included 31.4% increased head size, 25.7% congestive heart failure, 12.9% neurological deficits, 10% seizures, 9.3% prominence of facial veins, and 8.9% developmental delay. A total of 339 patients underwent endovascular treatment (84.8%) with an average of 2.1 procedures per patient. The embolization technique was defined by transarterial access and glue material. Radiological occlusion was complete in 62.3% of the patients. The most frequent periprocedural incidents included hemorrhagic events (28.4%), embolization material migration (25.7%), and death (22%). The functional outcome was good in 68% of the surviving patients. The average follow-up time was 43.18 months. High heterogeneity was found in all outcomes but mortality rate. Conclusions: The angioarchitecture of VGAMs is significantly important when planning endovascular treatment and may have an influence on functional outcomes. More research into endovascular techniques and the risks of periprocedural complications must be performed. Indeed, a homogeneous protocol for the assessment of surviving VGAM patients during follow-up is necessary. Full article