Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β₂-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.     

Zero-Valent Iron Nanoparticles Remediate Nickel-Contaminated Aqueous Solutions and Biosolids-Amended Agricultural Soil

Nickel (Ni⁺²) accumulation in wastewater treatment sludge poses a potential environmental risk with biosolids-land application. An incubation experiment was conducted to evaluate the effect of nanoparticles of zero-valent iron (nZVI) on Ni⁺² sorption in biosolids-treated agricultural soils. Two application rates of biosolids (0, 5%, w/w) and four treatment levels (0, 1, 5, and 10 g/kg) of nZVI were examined, either separately or interactively. The results of this study showed significant differences in Ni⁺² sorption capacity between different nZVI treatments. The initial Ni⁺² concentration in biosolids-amended soil significantly affected Ni sorption in the soil treated with nZVI. The “H-shape” of sorption isotherm in nZVI-treated soil reflects strong interaction between the Ni concentration and the nZVI treatment, while the C-shape of sorption isotherm in biosolids-amended soil without the nZVI treatment indicates intermediate affinity for Ni⁺² sorption. Nickel retention in soil was increased with the increase of nZVI levels. The removal efficiency of Ni⁺² by nZVI from solution was increased with the increase of pH from 5 to 11 and reached a maximum of 99.56% at pH 11 and nZVI treatment of 10 g/kg. The Ni⁺² desorption rate decreased from 92 to 7, 4, and 1% with increasing nZVI treatment levels from 0 to 1, 5, and 10 g/kg, respectively, with a soil Ni⁺² concentration of 50 mg/L. The maximum adsorption capacity (𝑞_max) of 10 g/kg nZVI-treated soil was 333.3 mg/g, which was much higher than those from the other treatments of 0 (5 mg/g), 1 (25 mg/g), and 5 g/kg (125 mg/g). The underlying mechanism for Ni⁺² immobilization using nZVI in an aquatic environment is controlled by a sorption process, reduction of metal ion to zero-valent metal, as well as (co)precipitation. Moreover, increasing the nZVI treatment level in biosolids-amended soil significantly decreased bioavailable Ni⁺² concentrations in the soil.     

Effects of a yoga intervention on lipid profiles of diabetes patients with dyslipidemia

ObjectiveThe present study was conducted to assess the effectiveness of yoga in the management of dyslipidemia in patients of type 2 diabetes mellitus.MethodsThis randomized parallel study was carried out in Medical College Trivandrum, Kerala, India. Hundred type 2 diabetics with dyslipidemia were randomized into control and yoga groups. The control group was prescribed oral hypoglycemic drugs. The yoga group practiced yoga daily for 1 h duration along with oral hypoglycemic drugs for 3 months. The lipid profiles of both the groups were compared at the start and at the end of 3 months.ResultsAfter intervention with yoga for a period of 3 months the study group showed a decrease in total cholesterol, triglycerides and LDL, with an improvement in HDL.ConclusionYoga, being a lifestyle incorporating exercise and stress management training, targets the elevated lipid levels in patients with diabetes through integrated approaches.     

Quality of Life Assessment in Trials of Revascularization for Chronic Stable Angina: Insights from ORBITA and the Implications of Blinding

Cardiovascular Drugs and Therapy - The main aims of therapy in chronic stable angina are to reduce the risk of myocardial infarction and death and improve symptoms and quality of life (QoL)....     

Characteristics,evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study

Clinical Rheumatology - To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84...     

The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5 h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value? 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value?=?0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level.

     

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro-protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX-induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg⁻¹ day⁻¹, PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg⁻¹ day⁻¹ REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX-treated rats. However, REB prevented MTX-induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF-2 protein and upregulated the expression of both SIRT-1 and FOXO-3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF-κB-p65 and TLR-4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.