New butyrylcholinesterase inhibitory steroid and peroxy acid from Leucas urticifolia

A new steroid leucisterol (1) and a new peroxy acid urticic acid (2) along with methoxybenzyl benzoate (3), 4-hydroxy benzoic acid (4), beta-sitosterol (5), and ursolic acid (6), have been isolated from the chloroform soluble fraction of the whole plant of Leucas urticifolia. Their structures were elucidated on the basis of nuclear magnetic resonance (1D and 2D NMR) spectral data. Leucisterol showed potent inhibitory activity against butyrylcholinesterase enzyme.     

Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin

Context: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.

Objective: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.

Materials and Methods: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using ¹HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.

Results and discussion: Findings showed that vesicles were able to entrap up to 67.82?±?1.27% of the drug, and were rounded in shape with a size around 202.73?±?5.30?nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500?mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.

Conclusion: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.     

Renal cellular hypoxia in adenine‐induced chronic kidney disease

We determined whether adenine‐induced chronic kidney disease (CKD) in rats is associated with renal tissue hypoxia. Adenine (100 mg) or its vehicle was administered to male Sprague‐Dawley rats, daily by oral gavage, over a 15‐day period. Renal function was assessed before, and 7 and 14 days after, adenine treatment commenced, by collection of a 24‐hour urine sample and a blood sample from the tail vein. On day 15, arterial pressure was measured in conscious rats via the tail artery. Renal tissue hypoxia was then assessed by pimonidazole adduct immunohistochemistry and fibrosis was assessed by staining tissue with picrosirius red and Masson's trichrome. CKD was evident within 7 days of commencing adenine treatment, as demonstrated by increased urinary albumin to creatinine ratio (30 ± 12‐fold). By day 14 of adenine treatment plasma creatinine concentration was more than 7‐fold greater, and plasma urea more than 5‐fold greater, than their baseline levels. On day 15, adenine‐treated rats had slightly elevated mean arterial pressure (8 mmHg), anaemia and renomegaly. Kidneys of adenine‐treated rats were characterised by the presence of tubular casts, dilated tubules, expansion of the interstitial space, accumulation of collagen, and tubulointerstitial hypoxia. Pimonidazole staining (hypoxia) co‐localised with fibrosis and was present in both patent and occluded tubules. We conclude that renal tissue hypoxia develops rapidly in adenine‐induced CKD. This model, therefore, should prove useful for examination of the temporal and spatial relationships between tubulointerstitial hypoxia and the development of CKD, and thus the testing of the ‘chronic hypoxia hypothesis’.     

Recent Advances in the Surface Functionalization of Nanomaterials for Antimicrobial Applications

Innovations in nanotechnology have had an immense impact on medicine, such as in drug delivery, tissue engineering, and medical devices that combat different pathogens. The pathogens that may cause biofilm-associated nosocomial diseases are multidrug-resistant (MDR) bacteria, such as Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), including both Gram-positive and Gram-negative bacterial species. About 65–80% of infections are caused by biofilm-associated pathogens creating a move in the international community toward developing antimicrobial therapies to eliminate such pathogenic infections. Several nanomaterials (NMs) have been discovered and significantly employed in various antipathogenic therapies. These NMs have unique properties of singlet oxygen production, high absorption of near-infrared irradiation, and reasonable conversion of light to heat. In this review, functionalized NPs that combat different pathogenic infections are introduced. This review highlights NMs that combat infections caused by multidrug-resistant (MDR) and other pathogenic microorganisms. It also highlights the biomedical application of NPs with regard to antipathogenic activities.     

内镜支架置入新技术治疗幽门良性狭窄的初步观察（含视频）

2017年6月—2019年9月,5例良性重度幽门狭窄患者在郑州大学第一附属医院接受了内镜下全覆膜支架置入新技术治疗,5例均成功完成幽门处全覆膜支架置入,无并发症发生,术后行上消化道造影显示支架位置良好、造影剂通过顺利。5例患者于术后1～3 d开始进流食,进食后均无呕吐、腹痛、腹泻等症状出现,随访期间均有不同程度的体重增加,营养状态获得明显改善。4例于术后3～4个月行支架取出术;余1例于术后3个月发现支架移位至胃内,取出支架后观察幽门口略狭窄,行球囊扩张术+黏膜切开术。随后5例继续随访3个月,均无症状反复及再狭窄。以上结果初步证实,内镜下全覆膜支架置入新技术治疗良性幽门狭窄安全、有效。     

DFT study of superhalogen and superalkali doped graphitic carbon nitride and its non-linear optical properties

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl₄) and superalkali (NLi₄) doped graphitic carbon nitride (GCN). It is noted that the geometries of doped GCN are sufficiently stable. The energy gap for GCN is 3.89 and it reduces to 0.53 eV in our designed molecule G4. Change in the dipole and transition dipole moment is observed along with small transition energies which are responsible for higher hyperpolarizabilities. Doped GCN has larger first and second hyperpolarizabilities which are basic requirements for NLO response. The second hyperpolarizability of GCN enhances from 1.59 × 10⁴ to 2.53 × 10⁸ au when doping with BCl₄ and NLi₄. TD-DFT calculations show the absorption maxima of doped GCN range from 700 nm to 1350 nm. EDDM analysis provides information on electronic distribution from excited to ground state. All these consequences show doped GCN can be a promising NLO material.

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl₄) and superalkali (NLi₄) doped graphitic carbon nitride (GCN).     

Exploration of CH⋯F & CF⋯H mediated supramolecular arrangements into fluorinated terphenyls and theoretical prediction of their third-order nonlinear optical response

In the present study, three novel fluorinated terphenyl compounds i.e., 2′,4,4′′,5′-tetrafluoro-1,1'':4′,1′′-terphenyl (1), 2′,5′-difluoro-1,1'':4′,1′′-terphenyl (2) and 2′,5′-difluro-4,4′′-diphenoxy-1,1:4′,1′′-terphenyl (3) have been synthesized by Suzuki Miyaura method. Single crystal XRD study reveals ð-ð stacking stabilization in molecular packing along with F⋯H and F⋯C interactions. This computational quantum chemical exploration was also done by using density functional theory (DFT) methods. The comparison of experimental (SC-XRD) and theoretical (DFT) investigations on structural parameters have been reported which shows reasonable agreements. Hirshfeld surface analysis explores the strength of intermolecular interactions present in the synthesized compounds. A substantial computational analysis of synthesized compounds is done for their optoelectronic and third-order nonlinear optical properties. The third-order NLO study was performed at M06/6-311G* level of theory. A comparative analysis of third-order polarizability of studied compounds is done with that of para-nitroaniline (p-NA) molecule which is often considered as a prototype NLO molecule. The third-order NLO analysis results suggest that all investigated compounds 1, 2 and 3 have significant potential as efficient third-order NLO molecules as compared to p-NA. The studied compounds 1, 2 and 3 possess about 13.7 times, 5.2 times and 5.17 times larger third-order polarizability amplitudes than that of p-NA (25.45 × 10⁻³⁶ esu) as calculated at same M06/6-311G* levels of theory. Time-dependent density functional theory (TD-DFT) calculations are performed for electronic excitation energies and their oscillator strengths. The studies of frontier molecular orbitals (FMO) analysis, total and partial density of states (DOS) were performed to investigate the intramolecular charge transfer (ICT) process in the entitled compounds.

Three novel fluorinated terphenyls were synthesized by a Suzuki Miyaura method. DFT and TDDFT were performed to explore FMO, DOS analysis and third-order NLO properties. This may provide new ways to utilise fluorinated terphenyl compounds as advanced functional materials.     

Synthesis and Characterization of Manganese-Modified Black TiO2 Nanoparticles and Their Performance Evaluation for the Photodegradation of Phenolic Compounds from Wastewater

The release of phenolic-contaminated treated palm oil mill effluent (TPOME) poses a severe threat to human and environmental health. In this work, manganese-modified black TiO₂ (Mn-B-TiO₂) was produced for the photodegradation of high concentrations of total phenolic compounds from TPOME. A modified glycerol-assisted technique was used to synthesize visible-light-sensitive black TiO₂ nanoparticles (NPs), which were then calcined at 300 °C for 60 min for conversion to anatase crystalline phase. The black TiO₂ was further modified with manganese by utilizing a wet impregnation technique. Visible light absorption, charge carrier separation, and electron–hole pair recombination suppression were all improved when the band structure of TiO₂ was tuned by producing Ti³⁺ defect states. As a result of the enhanced optical and electrical characteristics of black TiO₂ NPs, phenolic compounds were removed from TPOME at a rate of 48.17%, which is 2.6 times higher than P25 (18%). When Mn was added to black TiO₂ NPs, the Ti ion in the TiO₂ lattice was replaced by Mn, causing a large redshift of the optical absorption edges and enhanced photodegradation of phenolic compounds from TPOME. The photodegradation efficiency of phenolic compounds by Mn-B-TiO₂ improved to 60.12% from 48.17% at 0.3 wt% Mn doping concentration. The removal efficiency of phenolic compounds from TPOME diminished when Mn doping exceeded the optimum threshold (0.3 wt%). According to the findings, Mn-modified black TiO₂ NPs are the most effective, as they combine the advantages of both black TiO₂ and Mn doping.     

Outcomes of patients with multiple sclerosis at a neurorehabilitation unit in Saudi Arabia

Objectives:To assess the impact of inpatient multidisciplinary rehabilitation on a Saudi Arabian population of patients with multiple sclerosis (MS).Methods:We retrospectively analyzed the data of patients with MS who underwent inpatient rehabilitation between 2009 and 2015 at King Fahad Medical City (KFMC). Differences in Functional Independence Measure (FIM) scores (used in rehabilitation settings to assess the functional independence of patients) and length of stay (LOS) were measured between patients of different ages, sexes, and types of MS and analyzed using the independent t-test. The Pearson correlation coefficient was used to investigate the correlation between FIM, LOS, and other variables.Results:In total, 24 patients were identified, with an average age of 36 years. The average age at disease onset was 31 years. Disease duration ranged from 1-20 years, with a mean of 7 years. The most common type of MS was relapsing-remitting (45.8%). The mean FIM score at admission was 77.5 and at discharge 97.25. Functional independence measure gain ranged from 2-51, with a mean of 18.58. Functional independence measure efficiency (FIM gain divided by LOS) ranged between 0.09-0.95. The length of stay ranged between 21-95 days, with a mean of 37.79 days. There was a significant association between age and FIM efficiency (p=0.043).Conclusions:Inpatient rehabilitation is an important intervention that improves the functional independence of patients with chronic MS.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease with a female preponderance and an estimated prevalence of 30-190 cases per 100,000 people in Europe.1 Because of its early onset, progressive course, and long survival time, MS can lead to long-term disability with a significant negative impact on personal and social life.2,3 Among neurologic diseases, it is the third most common cause of disability, with 50% of patients requiring a walking aid and 10% requiring a wheelchair within 15 years of onset; within 25 years of onset, more than 90% of patients experience significant functional impairments.4,5 Life expectancy in patients with MS is reduced by about 5-10 years compared with age-matched individuals without MS.6 Around 2 million people worldwide are affected by MS.7 In young adults, this disabling neurodegenerative disease of the central nervous system is considered the leading cause of non-traumatic disability.8 In the Middle East, the risk of MS has recently been reported to be moderate to high.9 The Kurtzke classification places the Middle East in a low-risk zone for MS; however, a moderate-to-high prevalence in areas within the region (31-55 cases per 100,000 individuals), especially among women, has recently been reported.10,11 Thus, MS represents a considerable burden to Middle Eastern countries. In the Kingdom of Saudi Arabia, the prevalence of MS is poorly documented. Reviews of epidemiologic studies have suggested that it is underdiagnosed and that its prevalence is increasing.10,11 A few studies have reported an increase in the prevalence of MS in the Kingdom of Saudi Arabia to 40/100,000 in 2008 from 25/100,000 in 1998.9,12 Likewise, there are no data on the effects of inpatient rehabilitation in the Arabian Peninsula. In the literature, common treatment strategies are based on a combination of pharmacotherapy and rehabilitation. In daily practice, multidisciplinary rehabilitation (MDR) is often recommended to patients with MS. However, the evidence regarding the outcomes of MDR is contradictory. Some trials have reported improvements in impairment and in the mental component of a health-related quality of life measure, but others have shown that MDR improves the experience of people with MS in terms of activity and participation without changing the level of impairment.13,14-16 The overall evidence on the efficacy of MDR is limited by variation in the clinical presentation of MS and problems associated with study methodology.13 In this study, we assessed the impact of short-term inpatient MDR in a Saudi-Arabian population of patients with MS to identify the clinical predictors of effective rehabilitation treatment. At KFMC, both inpatient and outpatient services are included in the neurorehabilitation program. King Fahad Medical City treats patients from all regions of the country, including those internally transferred from the National Neuroscience Institute within KFMC. The integrated neurorehabilitation program was deemed to meet the standards of the Commission on Accreditation of Rehabilitation Facilities.17     

Phytotherapy and physical therapy in the management of chronic prostatitis–chronic pelvic pain syndrome

International Urology and Nephrology - Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) is one of the four category prostatitis, and the prevalence is over 90–95% in prostatitis....