Statistical modeling, optimization and characterization of andrographolide loaded emulgel for its therapeutic application on skin cancer through enhancing its skin permeability.

Andrographolide is a natural diterpene lactone with multiple biological effects. In the present study, a total of 11 andrographolide-loaded emulgels (ANG 1- ANG 11) were prepared by emulsification and solvent evaporation method using flaxseed oil and xanthan gum in different ratios, as suggested by the Design-Expert software. A 2-factor-5-level design was employed with different responses including spreadability, extrudability, viscosity, and drug release after 1 h (h) and 24 h. Based on the Design-Expert software response, the optimized emulgel ANG 12 was formulated and evaluated. The 24 h In-vitro drug release was found to be 95.7 % following Higuchi kinetics. Ex-vivo skin retention of 784.78 ug/cm2 was observed during the study. MTT assay performed on Human epidermoid carcinoma (A-431) cells demonstrated cell growth arrest at G0/G1 and G2/M phase after 24 h of ANG 12 treatment (IC50: 11.5 µg/ml). The cellular permeability of ANG-12 was assessed by Fluorescein isothiocyanate (FITC) assay. Compared to untreated cells (0.54 % uptake) the ANG-12 treated cells had shown 87.17 % FITC permeation. The biocompatibility study performed on non-cancerous human dermal fibroblast cells (HDF cells) shows 91.54 % viability after 24 h of the treatment showing the non-toxic nature of ANG-12. Confocal imaging had shown a significant time-dependent increase in in-vivo cellular uptake with enhanced, progressive penetration of the emulgel into the skin. An in-vivo skin irritation study conducted on Swiss albino mice confirmed the safety aspects of the ANG 12. Hence, it can be concluded that nanoemulgel of andrographolide (ANG 12) could be a novel approach to treating skin cancer.

Selection of potential natural compounds for poly-ADP-ribose polymerase (PARP) inhibition in glioblastoma therapy by in silico screening methods.

Glioblastoma (GBM), the most prevalent brain tumor, is one of the least treatable malignancies due to its propensity for intracranial spread, high proliferative potential, and innate resistance to radiation and chemotherapy. Current GBM therapy is limited due to unfavorable, non-specific therapeutic effects in healthy cells and the difficulty of small molecules to penetrate the blood brain barrier (BBB) and reach the tumor microenvironment. Adding PARP-1 inhibitors inhibit DNA repair enzymes thereby increasing the cytotoxicity of anticancer agents. Hence, we aimed to discover potential naturally occurring PARP-1 inhibitors that can be utilized in the treatment of glioma by using multiple in silico tools like molecular docking, absorption, distribution, metabolism, and excretion (ADME) profile, pharmacophore modeling, and molecular dynamic (MD) simulations. Among 43 phytocompounds we screened, two of them (Ellagic acid and Naringin) were discovered to be bound to the catalytic site of PARP-1 with an affinity more remarkable than commercially available PARP-1 inhibitors (Talazoparib, Niraparib, and Rucaparib) except Olaparib. The molecular interactions were analyzed, and data shows that bound entity attained a conserved domain via hydrogen bond interactions, polar interactions, and π-π stacking. Pharmacophore modeling studies showed electronic and steric features of ligands responsible for supramolecular interaction with PARP-1. ADME properties were studied, to assess drug-likeness, hydrophilic nature, hydrophobicity, brain permeability, and oral bioavailability of the natural PARP-1 inhibitors. The simulation study demonstrated the development of a stable complex between Naringin, Ellagic acid, and PARP-1 protein. Moreover, cell culture studies and animal investigations are essential to determine pharmacokinetics and pharmacodynamics.

Profile of Mucormycosis Cases from a Network of Hospitals in North India Amidst COVID-19 Pandemic

Incidence of mucormycosis suddenly surged in India after the second wave of COVID-19. This is a crippling disease and needs to be studied in detail to understand the disease, its course, and the outcomes. Between 1st March and 15th July 2021, our network of hospitals in North India received a total of 155 cases of COVID-associated mucormycosis cases as all of them reported affliction by COVID-19 earlier or concurrent. Their records were retrieved from the Electronic Health Records system of the hospitals and their demographics, clinical features, treatments, and outcomes were studied. More than 80% (125 cases) had proven disease and the remaining 30 were categorized as possible mucormycosis as per the EORTC criteria. More than two-thirds (69.0%) of the cases were males and the mean age was 53 years for either sex. Nearly two-thirds (64.5%) had symptoms of nose and jaws and 42.6% had eye involvement. Some had multiple symptoms. As many as 78.7% had diabetes and 91.6% gave history of use of steroids during COVID-19 treatment. The primary surgery was functional endoscopic sinus surgery (FESS) (83.9%). Overall mortality was 16.8%, which is one-and-a-half times the mortality in hospitalized COVID-19 patients in the corresponding population. Occurrence of mucormycosis was associated with diabetes and use of steroids, but mortality was not associated with either of them. Cases undergoing surgery and on antifungal had steeply lower mortality (11.9% vs. 50.0%, P < 0.001) than those who were exclusively on antifungal drugs. Treatment by different drugs did not make much of a difference in mortality.

Clinical applications and performance of intelligent systems in dental and maxillofacial radiology: A review

Intelligent systems (i.e., artificial intelligence), particularly deep learning, are machines able to mimic the cognitive functions of humans to perform tasks of problem-solving and learning. This field deals with computational models that can think and act intelligently, like the human brain, and construct algorithms that can learn from data to make predictions. Artificial intelligence is becoming important in radiology due to its ability to detect abnormalities in radiographic images that are unnoticed by the naked human eye. These systems have reduced radiologists' workload by rapidly recording and presenting data, and thereby monitoring the treatment response with a reduced risk of cognitive bias. Intelligent systems have an important role to play and could be used by dentists as an adjunct to other imaging modalities in making appropriate diagnoses and treatment plans. In the field of maxillofacial radiology, these systems have shown promise for the interpretation of complex images, accurate localization of landmarks, characterization of bone architecture, estimation of oral cancer risk, and the assessment of metastatic lymph nodes, periapical pathologies, and maxillary sinus pathologies. This review discusses the clinical applications and scope of intelligent systems such as machine learning, artificial intelligence, and deep learning programs in maxillofacial imaging.

Hemophagocytic Lymphohistiocytosis Masquerading as Acute Liver Failure: A Single Center Experience.

BACKGROUND/AIM: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening disorder of extreme inflammation and unregulated immune response which require prompt recognition and early introduction of definitive therapy. HLH can present with wide range of hepatic dysfunction ranging from mild elevation of transaminases to liver failure. This study is carried out to describe the clinical and laboratory presentation of HLH. METHODS: Patients who were diagnosed with HLH between January 2013 and December 2015 were retrospectively included in this study. RESULTS: Six patients were diagnosed as secondary HLH with median age of 28.5 years at diagnosis. All patients were presented with history of deep jaundice and high grade fever with pancytopenia and splenomegaly. Underlying diagnosis was viral infections in 4 and probable viral infection in remaining two. Bone marrow hemophagocytosis was present in 3 cases. Three patients were treated with corticosteroids only and one each with corticosteroids with cyclosporine or intravenous immunoglobulin (IVIG) and HLH treatment protocol. One patient died due to acute respiratory distress syndrome (ARDS); another patient died in follow-up due to respiratory failure due to pneumonia. CONCLUSIONS: HLH is rare and potentially life-threatening cause of prolonged fever, jaundice and pancytopenia. Early diagnosis and initiation of specific therapy can improve clinical outcome.

Achalasia Cardia Subtyping by High-Resolution Manometry Predicts the Therapeutic Outcome of Pneumatic Balloon Dilatation

BACKGROUND/AIMS: High-resolution manometry (HRM) with pressure topography is used to subtype achalasia cardia, which has therapeutic implications. The aim of this study was to compare the clinical characteristics, manometric variables and treatment outcomes among the achalasia subtypes based on the HRM findings. METHODS: The patients who underwent HRM at the Asian Institute of Gastroenterology, Hyderabad between January 2008 and January 2009 were enrolled. The patients with achalasia were categorized into 3 subtypes: type I - achalasia with minimum esophageal pressurization, type II - achalasia with esophageal compression and type III - achalasia with spasm. The clinical and manometric variables and treatment outcomes were compared. RESULTS: Eighty-nine out of the 900 patients who underwent HRM were diagnosed as achalasia cardia. Fifty-one patients with a minimum follow-up period of 6 months were included. Types I and II achalasia were diagnosed in 24 patients each and 3 patients were diagnosed as type III achalasia. Dysphagia and regurgitation were the main presenting symptoms in patients with types I and II achalasia. Patients with type III achalasia had high basal lower esophageal sphincter pressure and maximal esophageal pressurization when compared to types I and II. Most patients underwent pneumatic dilatation (type I, 22/24; type II, 20/24; type III, 3/3). Patients with type II had the best response to pneumatic dilatation (18/20, 90.0%) compared to types I (14/22, 63.3%) and III (1/3, 33.3%). CONCLUSIONS: The type II achalasia cardia showed the best response to pneumatic dilatation.

Extracorporeal shock wave lithotripsy and endotherapy for pancreatic calculi-a large single center experience.

AIM: Large pancreatic ductal calculi and pain are a feature of chronic calcific pancreatitis (CCP) in the tropics. This large single center study evaluates the role of extracorporeal shock wave lithotripsy (ESWL) in fragmentation of large pancreatic stones and relief of pain in patients with CCP. METHODS: Patients with CCP presenting with pain and large pancreatic duct (PD) calculi (>5 mm diameter) not amenable to extraction at routine endoscopic retrograde cholangio pancreatography (ERCP) were taken up for ESWL using a 3rd generation lithotripter. Stones in the head and body of pancreas were targeted at ESWL; 5,000 shocks were given per session. The calculi were fragmented to <3 mm size and then cleared by endotherapy. Pancreatic duct stents were deployed when indicated. A total of 1,006 patients underwent ESWL. Complete clearance was achieved in 762 (76%), partial clearance in 173 (17%) and unsuccessful in the rest. More than 962 (90%) of patients needed less than three sessions of ESWL. At 6 months, 711 (84%) of 846 patients who returned for follow up had significant relief of pain with a decrease in analgesic use. Complications were mild and minimal. CONCLUSION: ESWL is an effective and safe modality for fragmentation of large PD calculi in patients with CCP.