Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.
Abstract Objective: The study objective is to compare the pain frequency and mean hospital stay in patients with and without drain insertion, following laparoscopic cholecystectomy for acutely inflamed gallbladder. Methods: Randomized control trial was carried out in General Surgery Department Shifa International Hospital for a period of 1 year from October 2017 to October 2018. All patients with acutely inflamed gallbladder admitted underwent laparoscopic cholecystectomy using conventional 4 port method. Applying Lottery method patients were sorted into two groups; (Group A) – without drain and (Group B) – with drain. Post operatively parameters of pain and total hospital stay were assessed. Data was entered into a standard SPSS sheet version 15.0. Results: Mean age of patients in without drain (group A) was 52.00±14.84 years and in with drain (group B) was 47.50±18.28 years. In without drain (group A), there were 9 (30.0%) males and 21 (70.0%) females, mean VAS was 2.37±1.22, 16.7% (5 of 60 patients) had pain, and mean hospital stay was 1.93+/-0.79 days. In with drain (group B), 13 (43.3%) were males and 17 (56.7%) were females, mean VAS was 3.2 +/-1.36, 36.7% (11 of 60 patients) had pain and mean hospital stay was 3.17+/- 0.87 days. The difference between the two groups for mean VAS was significant (P<0.05), for mean hospital stay was significant (P<0.05) but for pain frequency was insignificant (P>0.05). Conclusions: It has been concluded that without drain, more appropriate results have been obtained as compared to drain. Clinical Trial Number: NCT04346550
Objective: To analyze radiological spectrum of HRCT in COVID-19 patients, clinically symptomatic but initially having negative RT-PCR. Study Design: Prospective cross sectional descriptive study. Place and Duration of Study: Radiology and Medicine Department, DHQ Hospital Rawalpindi, from June to November 2020 Methodology: The study included 90 patients presenting with clinical symptoms of COVID-19 but with negative RT-PCR. All patients underwent chest computed tomography (CT). Patients with positive COVID-19 RT-PCR test or serology on subsequent repeat test were included in the study. Patients having non COVID-19 HRCT features with negative RT-PCR were excluded from the study. Results: Out of 90 symptomatic, RT-PCR negative patients, 7 had normal chest CT. According to BSTI classification, 50 patients showed classic, 11 had probable and 22 had indeterminate features. Despite supportive clinical and CT features, 17 (18.89%) patients had negative RT-PCR tests on subsequent testing. Unilateral changes were in 8 (8.9%) and bilateral in 75 (83.3%). Most common finding was mixed pattern of peripherally distributed GGN and bronchocentric nodules in 37 (41.1%) patients. Consolidations were in 19 (21.1%), pure ground glass haze in 13 (14.4%), crazy paving in 4 (4.4%), fuzzy bands and arcades in 7 (7.8%), and subtle gravitational GGH in 3 (3.3%) patients. CT-SS classified 69 (76.7%) patients as mild, 10 (11.1%) as moderate and 4 (4.4%) as severe disease. Conclusions: HRCT with CTSS is an important tool for diagnosing and prognosticating COVID-19 infection despite negative RT-PCR, timely identifying and isolating COVID-19 cohorts preventing cross infection and also aiding in prompt symptomatic management.
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