Simeprevir is a new direct-acting antiviral drug used for the treatment of chronic hepatitis C. In this work, a simple, fast and economical chromatographic method was developed for the determination of simeprevir in the presence of its acidic and oxidative degradation products. The stress studies performed herein showed that simeprevir degraded under acidic and oxidative conditions but was stable under thermal and alkaline conditions. Chromatographic separation was achieved on a reversed-phase Eclipse XDB C18 column (4.6 × 150 mm, 5 μm). The mobile phase consisted of methanol-0.05 M ammonium acetate (pH 4) (90 : 10, v/v) and was used at a flow rate of 1 mL min−1. The column effluent was monitored at 237 nm. The calibration curve was linear over the concentration range of 0.1–20 μg mL−1. The relative standard deviations for the intra-day and inter-day precision were less than 2%, and good percentage recoveries that met the acceptance criteria of the International Conference on Harmonization (ICH) guidelines were obtained. The robustness was assessed using the Plackett–Burman design. The simeprevir degradation products were isolated by flash chromatography and confirmed by 1H NMR and LC-MS/MS techniques. The fully validated chromatographic method can be applied as a stability-indicating method for simeprevir and for routine analysis during quality control. Additionally, in silico toxicity prediction of the degradation products demonstrated a hepatotoxicity alert for DP 1, DP 2, DP 4 and DP 5 and a carcinogenicity alert for DP 3. In view of safety aspects, an in vitro cytotoxicity assay was carried out for simeprevir degradation products. They were found to be non-toxic in vitro at the tested concentrations.Simeprevir is a new direct-acting antiviral drug used for the treatment of chronic hepatitis C.相似文献
There is an increasing demand for age estimations of living persons who are involved in civil and criminal procedures but lack a valid birth certificate indicating their date of birth. Several studies have recommended the application of magnetic resonance imaging (MRI) and assessment of the stage of epiphyseal fusion in age estimation. This study involved retrospective MRI analysis of 335 cases (217 males and 118 females) whose ages ranged from 8 to 28 years (yrs). We assessed the degree of ossification of the proximal tibial epiphysis depending on the classifications of Schmeling and Kellinghaus used for the main stages (I, II, III, IV & V) and substages (IIa, b, c & IIIa, b, c). Significant differences between males and females at stages IIIc, IV and V (p < 0.001) were observed. Additionally, the ossification of the proximal tibial epiphyses occurred earlier in females than in males (2–4 yrs). The mean of ages in stage IV was approximately 18.6 yrs. in females and 22.5 yrs. in males, meaning that stage IV can be used as a valuable forensic marker to determine whether the person in question has reached the age of 18 yrs. We concluded that the application of MRI in the assessment of the ossification status of the proximal tibial epiphysis could be helpful in age estimation for various forensic purposes. 相似文献
Neurological Sciences - COVID-19 is a pandemic disease which predominantly affects the respiratory system with high critical care mortality and morbidity; however, it also causes multi-organ... 相似文献
Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1–17). Forty‐seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram‐negative infection (57.1%) was more prevalent than Gram‐positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram‐negative bacteria being the most common. 相似文献
BACKGROUND: Bullous skin lesions are characterised by the presence of intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a constant feature in these lesions, their immunophenotypic characterisation is still incomplete. AIM: To determine whether the development of bullous skin diseases is associated with changes in the inflammatory cell infiltrate. Materials and methods: 34 cases representing lesions with both intraepidermal and subepidermal bullae were examined using immunoperoxidase staining methods and antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells (CD3+), T cells with cytotoxic potential (T cell intracellular associated antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin (lesions) and an additional five cases of normal skin were also examined (controls). RESULTS: The transition from normal skin to lesional skin (lesions with intraepidermal and subepidermal bullae) was associated with a significant increase (p< or =0.05) in the density of total inflammatory cell infiltrate, CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+ -resting cytotoxic T cells and GRB+ T cells with cytotoxic activity. CONCLUSIONS: The increase in inflammatory cell infiltrate during the transition from normal to lesional skin may reflect the presence of an increased antigenicity of the lesional cells or a response to some basement membrane components. CD68+ and CD3+ cells, especially the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell-mediated immunity seems to have critical role in the development of these lesions. 相似文献
Inflammation is a complex biological process that is generally occurs in response to pathological triggers. Both neurodegenerative diseases and cancer have been linked to inflammation. The analgesic and anti‐inflammatory effects of cupressuflavone (CUF) isolated from Cupressus macrocarpa were examined. The analgesic effects of CUF (40, 80 and 160 mg/kg po) were assessed in the acetic acid‐induced writhing and hot plate models in mice with diclofenac sodium as the reference standard (100 mg/kg). CUF dose‐dependently inhibited the writhing response in mice by 25, 48, and 62%, at the three CUF doses with 160 mg/kg being equivalent to the diclofenac control. CUF dose‐dependently increased the hot plate model reaction time with a maximal effect after 120 min. In the carrageenan‐induced paw edema model of inflammation, CUF demonstrated anti‐inflammatory activity by inhibiting paw edema by 55, 60, and 64% at doses of 40, 80, and 160 mg/kg po, respectively. CUF also reduced the plasma pro‐inflammatory mediators PGE2 (44, 54, and 58%), TNF‐α (26, 37, and 53%), IL‐1β (19, 33, and 41%), and IL‐6 (32, 44, and 55%) at the three doses tested with the highest dose having similar effects to diclofenac sodium (100 mg/kg). This finding from this study indicates that CUF has both analgesic and anti‐inflammatory effects. 相似文献
The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin. 相似文献
Patients with uncontrolled type 1 diabetes mellitus (T1DM) are at a high risk for Ramadan fasting and are exempt from fasting; however, most still insist on fasting. The aim of this study was to examine glucose level fluctuations in those patients during Ramadan fasting using a real-time continuous glucose monitoring system (RT-CGMS).
Methods
This pilot study involved adult patients with uncontrolled T1DM (HbA1c?>?7%) who insisted on fasting during Ramadan in 2014 from Maternity and Children’s Hospital, Medina, Saudi Arabia. A Medtronic RT-CGMS was used to monitor the participants’ glucose levels for 3 consecutive days during fasting.
Results
The study included 22 patients (mean age 22?±?6?years, duration of diabetes 10.9?±?7.2?years, HbA1c level 9.3?±?1.2). All participants were using the basal-bolus insulin regimen, except for one patient who was on an insulin pump. Sensor glucose (SG) profiles typically followed a pattern that was characterized by an exaggerated increase after iftar, which was sustained overnight, and a second rapid rise after suhoor, with a prolonged glucose decay over the daylight hours. The average SG was 199?±?104.1?mg/dl, which was lower during fasting 188.4?±?103.41?mg/dl than during the eating hours 212.5?±?103.51?mg/dl (P?=?0.00). There was a higher rate of hyperglycemia (48%) than hypoglycemia (10%).
Conclusions
Patients with uncontrolled T1DM who fasted during Ramadan experienced a wide fluctuation of glucose levels between fasting and eating hours, exhibiting a greater tendency toward hyperglycemia. The long-term effects for this finding are not known and warrant further investigation. 相似文献
Cadmium (Cd) is one of the environmental risk factors for bone loss. The present study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed men were included as a control group. Current smokers represented 65% and 47.5% of the exposed and control groups, respectively.
The study aimed to investigate the hazard of occupational Cd exposure on bone health. This was achieved through measuring serum and urinary Cd, and calcium (Ca), in addition to serum osteoprotegerin (OPG) and estrogen receptor-α gene. Results showed significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed compared to the controls. Bony aches and joint pain were more prevalent among the exposed workers. Serum and urinary Cd increased in exposed smokers relative to control smokers. Also, serum OPG levels showed significant rise among exposed smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd level increased significantly in PP and pp genotypes in exposed workers compared to controls, while elevated levels of serum OPG was observed in PP and Pp genotypes in exposed workers relative to controls.
Urinary Cd exhibited significant rise in both PP and pp genotypes in exposed workers, while Ca excretion was elevated in pp genotype only. The study reflected an association of genetic predisposition and Cd exposure in progression of osteoporosis. Further research is needed to explain the mechanisms of Cd impact on bone. The role of smoking is important and hence smoking cessation programs are essential for sewage workers. 相似文献