6 research outputs found
The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
The effect of brain tomography findings on mortality in sniper shot head injuries
WOS: 000402863800013PubMed ID: 27903839Objectives Penetrating gunshot head injuries have a poor prognosis and require prompt care. Brain CT is a routine component of the standard evaluation of head wounds and suspected brain injury. We aimed to investigate the effect of brain CT findings on mortality in gunshot head injury patients who were admitted to our emergency department (ED) from the Syrian Civil War. Methods The study group comprised patients who were admitted to the ED with gunshot brain injury. Patients' GCS scores, prehospital intubations and brain CT findings were examined. Results 104 patients were included (92% male, mean age 25 years). Pneumocephalus, midline shift, penetrating head injury, patients with GCS scores <= 6 and patients who had to be intubated in the prehospital period were associated with higher mortality (p < 0.05). Discussion The results of this study demonstrated that pneumocephalus, midline shift, a penetrating head injury, GCS scores <= 6 and prehospital intubation are associated with high mortality, whereas patients with temporal bone fracture, perforating or single cerebral lobe head injury had a higher survival rates. The temporal bone has a relatively thin and smooth shape compared with the other skull bones so a bullet is less fragmented when it has penetrated the temporal bone, which could be a reason for the reduced cavitation effect. In perforating head injury, the bullet makes a second hole and so will have deposited less energy than a retained bullet with a consequent reduction in intracranial injury and mortality. Further studies are required to reach definitive conclusions
Dexpanthenol ameliorates lipopolysaccharide-induced cardiovascular toxicity by regulating the IL-6/HIF1α/VEGF pathway
Introduction: Lipopolysaccharide (Lps) is an essential component responsible for the virulence of gram-negative bacteria. Lps can cause damage to many organs, including the heart, kidneys, and lungs. Dexpanthenol (Dex) is an agent that exhibits anti-oxidative and anti-inflammatory effects and stimulates epithelialization. In this study, we aimed to investigate the effects of Dex on Lps-induced cardiovascular toxicity. Methods: Rats were divided into four groups: control, Lps (5 mg/kg, intraperitoneal), Dex (500 mg/kg, intraperitoneal), and Lps + Dex. The control group received saline intraperitoneally (i.p.) once daily for three days. The Lps group received saline i.p. once daily for three days and a single dose of Lps i.p. was administered on the third day. The Dex group received Dex i.p. once daily for three days and saline on the third day. The Lps + Dex group received Dex i.p. once daily for three days and a single dose of Lps i.p. on the third day. Heart and aortic tissues were taken for biochemical, histopathological, immunohistochemical, and genetic analysis. Results: Lps injection caused histopathological changes in both heart and aortic tissues and significantly increased total oxidant status and oxidative stress index levels. Interleukin-6, and Tumor necrosis factor-α mRNA expressions were significantly altered in heart and aorta, likely do to the anti-inflammatory and antioxidative effects of Dex. Furthermore, Dex affected Caspase-3 and Hypoxia-inducible factor 1-α staining patterns. Conclusions: Our results show that Dex treatment has a protective effect on Lps-induced cardiac and endothelial damage in rats by reducing inflammation, oxidative stress, and apoptosis
Salubrinal Ameliorates Inflammation and Neovascularization via the Caspase 3/Enos Signaling in an Alkaline-Induced Rat Corneal Neovascularization Model
Background and Objectives: Ocular alkaline burn is a clinical emergency that can cause permanent vision loss due to limbal stem cell deficiency and corneal neovascularization (CNV). Although the basic pathogenetic mechanisms are considered to be acute oxidative stress and corneal neovascularization triggered by inflammation, the underlying intracellular mechanisms have not been clearly elucidated. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress on inflammation and neovascularization, and the effect of the ER stress inhibitor salubrinal (SLB), as a novel treatment in a corneal alkaline burn model in rats. Methods: Chemical burns were created by cautery for 4 s using a rod coated with 75% silver nitrate and 25% potassium nitrate in the corneal center for the corneal neovascularization (CNV) model. Twenty-eight Wistar albino rats were divided into four groups: SHAM, CNV, CNV + SLB, and CNV + bevacizumab (BVC). After the CNV model was applied to the right eye, a single subconjunctival dose (0.05 mL) of 1 mg/kg salubrinal was injected into both eyes in the CNV + SLB group. A total of 1.25 mg/mL of subconjunctival BVC was administered to the CNV + BVC group. Fourteen days after experimental modeling and drug administration, half of the globes were placed in liquid nitrogen and stored at −20 °C until biochemical analysis. The remaining tissues were collected and fixed in 10% buffered formalin for histopathological and immunohistochemical analysis. Three qualitative agents from three different pathways were chosen: TNFR for inflammation, endothelial nitric oxide synthase (e-NOS) for vascular endothelial growth factor (VEGF)-mediated vascular permeability, and caspase-3 for cellular apoptosis. Results: Significantly lower caspase-3 and eNOS levels were detected in the CNV + SLB and CNV + BVC groups than in the CNV group. Additionally, histopathological evaluation revealed a significant decrease in neovascularization, inflammatory cell infiltration, and fibroblast activity in the CNV + SLB and CNV + BVC groups. The endoplasmic reticulum stress inhibitor, salubrinal, administered to the treatment group, attenuated apoptosis (caspase-3) and inflammation (e-NOS). In the control group (left eyes of the SLB group), salubrinal did not have a toxic effect on the healthy corneas. Conclusion: The ER stress pathway plays an important role in angiogenesis after alkaline corneal burns, and treatment with SLB modulates this pathway, reducing caspase-3 and eNOS levels. Further studies are needed to understand the molecular mechanisms altered by SLB-mediated therapy. The fact that more than one mechanism plays a role in the pathogenesis of CNV may require the use of more than one molecule in treatment. SLB has the potential to affect multiple steps in CNV pathogenesis, both in terms of reducing ER stress and regulating cellular homeostasis by inhibiting the core event of integrated stress response (ISR). Therefore, it can be used as a new treatment option and as a strengthening agent for existing treatments. Although blockade of intracellular organelle stress pathways has shown promising results in experimental studies, more in-depth research is needed before it can be used in routine practice. To the best of our knowledge, this study is the first to report the role of ER stress in corneal injury
Are Given Doses of Meropenem Adequate for Elderly Patients?
Introduction: Infections are major contributing factors to morbidity and mortality in the elderly. Aging affects various aspects of antibiotic pharmacokinetics, including absorption, distribution, and elimination. Maintaining adequate antibiotic concentrations is crucial in elderly individuals due to the heightened risk of treatment inadequacy. In this study, our objective was to investigate the plasma concentrations of meropenem, a commonly utilized antibiotic in elderly populations, and assess the impact of age on these measurements.
Materials and Methods: In this prospective observational study, we analyzed meropenem levels in a total of 177 blood samples obtained from 59 patients aged 65 and older. These patients were under the care of inpatient services outside the intensive care unit. Meropenem treatment was administered through intermittent infusions of 1 g in 0.5 hours every eight hours. A total of three blood samples were collected from each patient. These samples were collected on the third day of meropenem treatment, just before the next dose, at 30 and 120 minutes after the first dose. Plasma meropenem level was quantified using high-performance liquid chromatography-ultraviolet analysis. To determine the effect of age on the results, the obtained data were compared with the patient characteristics and laboratory parameters.
Results: Our results showed that in the first samples (Ctrough) plasma antibiotic concentrations exceeded the MIC in 20.3% of patients, while 79.7% remained at the subtherapeutic level. In the second (Cmax) and third samples (Cmid) 5.1% and 1.7% of patients remained at the subtherapeutic level, respectively. The plasma meropenem level was 8 mg/L and above in participants with four and more comorbidities, and this result demonstrated statistical significance (p< 0.05).
Conclusion: Current guidelines for beta-lactam antibiotics do not provide predictable trough antibiotic concentrations in older adults hospitalized for infections. There is a need for predictive factors to inform antibiotic dosing in the elderly population, and a greater emphasis on therapeutic drug monitoring of beta-lactams in these patients would be beneficial