Advanced glycation end-products (AGEs) resulting from non-enzymatic glycation are one of the major factors implicated in secondary complications of diabetes. Scientists are focusing on discovering new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. A number of natural and synthetic compounds have been proposed as AGE inhibitors. In this study, we investigated the inhibitory effects of AgNPs (silver nanoparticles) in AGEs formation. AgNPs (~30.5 nm) synthesized from Aloe Vera leaf extract were characterized using UV-Vis spectroscopy, energy-dispersive X-ray spectroscopy (EDX), high resolution-transmission electron microscopy, X-ray diffraction and dynamic light scattering (DLS) techniques. The inhibitory effects of AgNPs on AGEs formation were evaluated by investigating the degree of reactivity of free amino groups (lysine and arginine residues), protein-bound carbonyl and carboxymethyl lysine (CML) content, and the effects on protein structure using various physicochemical techniques. The results showed that AgNPs significantly inhibit AGEs formation in a concentration dependent manner and that AgNPs have a positive effect on protein structure. These findings strongly suggest that AgNPs may play a therapeutic role in diabetes-related complications.
Introduction. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Corona Virus-2 (SARS-CoV-2). The disease was first identified in December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019–2020 corona virus pandemic. SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have a zoonotic origin. The virus is primarily spread between people during close contact, often via small droplets produced by coughing, sneezing or talking. People may also become infected by touching a contaminated surface and then touching their face. COVID-19 patients currently remain the primary source of infection. An epidemiological survey indicated that the general population is susceptible to SARS-CoV-2. The spectrum of this disease ranges from mild to life-threatening. Fever is the most common symptom, although older people and those with comorbidities may experience fever later in the disease. Other common symptoms include cough, loss of appetite, fatigue, shortness of breath, sputum production, and muscle and joint pains. Symptoms such as nausea, vomiting and diarrhea have been observed in varying percentages. Some cases might progress promptly to acute respiratory distress syndrome (ARDS) and/or multiple organ function failure. Asymptomatic carriers and those in the incubation period may also be infectious. Aim. To determine the epidemiological and clinical characteristics of patients presenting with COVID-19 at the screening clinic of a tertiary care hospital in Peshawar, Pakistan. Methodology. In this descriptive study, we analysed data of patients presenting to a newly established Covid-19 screening clinic in Rehman Medical Institute. Anyone who reported with new onset fever and/or cough was tested for SARS-CoV-2 in the screening clinic. We documented and analysed demographic, epidemiological and clinical characteristics, which included age, sex, travel history, clinical features, comorbidities and laboratory data of patients confirmed by real-time reverse-transcription (RT)-PCR at Rehman Medical Institute, Peshawar, Pakistan from 15 March till 21 April 2020. Paired specimens of throat swabs and nasal swabs were obtained from 845 patients, ribonucleic acid (RNA) was extracted and tested for SARS-CoV-2 by the RT-PCR assay. Results. A total of 845 specimens were taken as described above. The positive rate for SARS-CoV-2 was about 14.3%. Male and older population had a significantly higher positive rate. Of the 121 patients infected with SARS-CoV-2, the mean age was 43.19 years (sd, 17.57) and the infections were more frequent among male gender accounting for 85 (70.25 %) patients. Common symptoms included fever (88 patients, 72 %), cough (72 patients, 59.5 %) and shortness of breath (69 patients, 57 %). Twenty-two (18 %) patients had recent travel history outside Pakistan in the previous 14 days, the majority of whom had returned back from Saudi Arabia. Conclusion. In this single-centre, prospective, descriptive study, fever, cough and shortness of breath were the most common symptoms. Old age (>50 years), chronic underlying comorbidities and travel history may be risk factors. Therefore, we concluded that viral nucleic acid amplification tests (NAAT) played an important role in identifying SARS-CoV-2 infection in a screening clinic, which helped with isolation and cohorting of these patients.
The use of successive generations of beta-lactams has selected successive generations of beta-lactamases including CTX-M ESBLs, AmpC beta-lactamases, and KPC carbapenamases in Enterobacteriaceae. Moreover, this cephalosporin resistance, along with rising resistance to fluoroquinolones, is now driving the use of carbapenems and unfortunately the carbapenem resistance has emerged markedly, especially in Acinetobacter spp. due to OXA- and metallo-carbapenemases. The industry responded to the challenge of rising resistance and recently developed some novel beta-lactams such as ceftobiprole, ceftaroline etc. and many beta-lactam compounds, including beta-lactamase-inhibitors, such as BMS-247243, S-3578, RWJ-54428, CS-023, SMP-601, NXL 104, BAL 30376, LK 157, and so on are under trials. This review provides the comprehensive accounts of the developments in penicillins, cephalosporins, carbapenems, and beta-lactamase-inhibitors, and the insight about medicinal chemistry, mechanism(s) of action and resistance, potential strategies to overcome resistance due to beta-lactamases, and also the recent advancements in the development of newer beta-lactam compounds; some of which are still under trials and yet to be classified. This review will fill the gap since previously published reviews and will serve as a comprehensive update on the current topic.
Development of multidrug resistance among pathogens has become a global problem for chemotherapy of bacterial infections. Extended-spectrum β-lactamase- (ESβL-) producing enteric bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are the two major groups of problematic MDR bacteria that have evolved rapidly in the recent past. In this study, the aqueous extract of Murraya koenigii leaves was used for synthesis of silver nanoparticles. The synthesized MK-AgNPs were characterized using UV-vis spectroscopy, FTIR, XRD, SEM, and TEM, and their antibacterial potential was evaluated on multiple ESβL-producing enteric bacteria and MRSA. The nanoparticles were predominantly found to be spheroidal with particle size distribution in the range of 5–20 nm. There was 60.86% silver content in MK-AgNPs. Evaluation of antibacterial activity by the disc-diffusion assay revealed that MK-AgNPs effectively inhibited the growth of test pathogens with varying sized zones of inhibition. The MICs of MK-AgNPs against both MRSA and methicillin-sensitive S. aureus (MSSA) strains were 32 μg/ml, while for ESβL-producing E. coli, it ranged from 32 to 64 μg/ml. The control strain of E. coli (ECS) was relatively more sensitive with an MIC of 16 μg/ml. The MBCs were in accordance with the respective MICs. Analysis of growth kinetics revealed that the growth of all tested S. aureus strains was inhibited (∼90%) in presence of 32 μg/ml of MK-AgNPs. The sensitive strain of E. coli (ECS) showed least resistance to MK-AgNPs with >81% inhibition at 16 μg/ml. The present investigation revealed an encouraging result on in vitro efficacy of green synthesized MK-AgNPs and needed further in vivo assessment for its therapeutic efficacy against MDR bacteria.
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