Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors

A series of pyrano[3,2 c]quinoline was evaluated for its in vivo efficacy as TNF‐α inhibitor using LPS, phosphodiesterase (PDE)‐4, and CIA assays in different mice/rat models. The synthesis was performed using one‐pot multicomponent condensation between 2,4‐dihydroxy‐1‐methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. In vivo efficacy of the title compounds was evaluated using LPS assay in BALB/c mice, PDE4 inhibition in ketamine–xylazine‐induced anesthetize SD rats, and CIA assay was performed in DBA/1J mice as per the standard literature protocols. The outcome of the study revealed that compound 4v was found to be most promising candidate of the series. It was efficacious with 48.8 ± 13.0% inhibition of TNF‐α release at 100 mg/kg p.o., in the LPS assay in Balb/c mice model. It was effective in PDE4 assay in ketamine–xylazine‐induced anesthetize SD rats with duration of 38.3 ± 4.5 min for reversal of anesthetic effect and also showed significant inhibition of PDE4 in salbutamol treated U937 cell assay. It was also abolished TNF‐α induced phosphorylation and degradation of IκBα. Ultimately, its effect on CIA‐related bone and cartilage damage was found statistically similar to Enbrel.     

Effect of extracts from Phyllanthus watsonii Airy Shaw on cell apoptosis in cultured human breast cancer MCF-7 cells

Species of Phyllanthus have traditionally been used for hundreds of years for treating many ailments including diabetes, anemia, bronchitis and hepatitis. The present study aims to investigate the cytotoxic and apoptotic effects of methanol (PWM), hexane (PWH) and ethyl acetate (PWE) extracts from the leaves of the endemic plant Phyllanthus watsonii Airy Shaw (Phyllanthaceae) on MCF-7 human breast cancer cells. We observed that the PWM, PWH and PWE extracts were cytotoxic and selectively inhibited the growth and proliferation of MCF-7 cells compared to untreated control in a dose dependent manner with an IC₅₀ of 12.7 ± 4.65, 7.9 ± 0.60 and 7.7 ± 0.29 μg/ml, respectively. However, the extracts were not toxic at these concentrations to normal human lung fibroblast MRC-5 cells. Cell death induced by PWM, PWH and PWE extracts were mainly due to apoptosis which was characterized by apoptotic morphological changes and a nuclear DNA fragmentation. Caspase-3 activation following P. watsonii extracts treatment was also evident for apoptotic cell death which was preceded by an S phase cell cycle perturbation. The results suggested that the cytotoxic activity of P. watsonii extracts was related to an early event of cell cycle perturbation and a later event of apoptosis. Hence, P. watsonii displays potential to be further exploited in the discovery and development of new anticancer agents.     

Hello,can you hear me? Orthopaedic clinic telephone consultations in the COVID-19 era- a patient and clinician perspective

BACKGROUNDThe coronavirus disease 2019 (COVID-19) pandemic has resulted in seismic changes in healthcare delivery. As a result of this, hospital footfall required to be reduced due to increased risk of transmission of infection. To ensure patients can safely access healthcare, we introduced orthopaedic clinic telephone consultations in our busy district general hospital.AIMTo investigate patients’ and clinicians’ perspective of telephone consultations during COVID-19, and whether this method of consultation could be a viable option in the post- pandemic future. METHODSThis is a single centre, prospective study conducted in a busy National Health Service district general hospital. In May 2020, 100 non- consecutive adult patients were contacted by independent investigators within 48 h of their orthopaedic clinic telephone consultation to complete a telephone satisfaction questionnaire. The questions assessed satisfaction regarding various aspects of the consultation including overall satisfaction and willingness to use this approach long term. Satisfaction and perspective of 25 clinicians conducting these telephone consultations was also assessed via an online survey tool.RESULTS93% of patients were overall satisfied with telephone consultations and 79% were willing to continue this method of consultation post- pandemic. Patients found telephone consultations to reduce personal cost and inconvenience associated with attending a hospital appointment. 72% of clinicians reported overall satisfaction with this service and 80% agreed that telephone consultations should be used in the future. The majority found it less laborious in time and administration in comparison to face to face consultations. Patients and clinicians expressed their desire for video consultations as a method of further improving their experience with remote consultations.CONCLUSIONOur study has shown that telephone consultations are a safe and rapid method of adaptation to the COVID-19 pandemic, achieving the aim of reducing hospital footfall. This method of consultation has resulted in immense clinician and patient satisfaction. Our findings suggest that this tool has benefits in post pandemic healthcare delivery. It has also highlighted that telephone consultations can act as a steppingstone to the introduction of the more complex platform of video consulting.     

Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: A report of three cases

Sepsis with multi organ dysfunction syndrome (MODS) is the most common cause of death in patients in noncoronary intensive care units. Currently, there are no specific treatments that reduce mortality in patients with sepsis and MODS. We report three patients who received therapeutic plasma exchange (TPE) for sepsis with MODS who completely recovered. The first patient, a 3‐year‐old male presented with Methicillin‐resistant Staphylococcus aureus‐associated respiratory, renal, coagulation, hepatic, and neurologic dysfunction. After 5 TPEs, the patient fully recovered. The second patient was a 36‐year‐old pregnant female who developed MODS at 22 weeks of gestation. She had developed respiratory, hepatic, renal, cardiovascular, neurologic, and coagulation dysfunction following pneumonia and concurrent urinary tract infection resulting in an intrauterine fetal demise. After 8 TPEs, the patient was discharged home with only mild residual hepatic dysfunction. The third patient, a 50‐year‐old female with a history of seizure disorder, was found unresponsive in over 100°F heat and diagnosed with Staphylococcus aureus‐associated MODS. Her respiratory, coagulation, neurologic, renal, and hepatic systems were affected. The patient underwent 6 TPEs after which she had marked improvement. In conclusion, TPE may be an effective adjunct therapy in MODS by possibly removing toxic mediators and replacing deficient factors using donor plasma. J. Clin. Apheresis 29:127–131, 2014. © 2013 Wiley Periodicals, Inc.