Scintigraphic Studies Research Articles

IMMU-15. QUANTIFYING INTRATHECAL DRUG DELIVERY UTILIZING PROGRAMMABLE VENTRICULOPERITONEAL SHUNTS

BackgroundProgrammable ventriculoperitoneal (pVP) shunts are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of thecal space drug concentrations with minimization in the peritoneum. Drug delivery quantification using several types of pVP shunts has not been reported. MethodsWe performed a retrospective analysis on patients with CNS tumors and pVP shunts at Memorial Sloan Kettering Cancer Center from 2003–2020, noting shunt model. CSF flow through the pVP shunt was evaluated using In-111-DTPA scintigraphy at approximately 4 hours and 24 hours after injection. pVP shunts were calibrated pre-injection to minimize peritoneal flow and re-calibrated to baseline setting 4–5 hours following injection. Scintigraphy studies quantified ventricular-thecal and peritoneal drug activity at these 2 time points. ResultsTwenty-one CSF flow studies were administered to 15 patients, ages 1–27 years. Diagnoses included medulloblastoma (N=10), metastatic neuroblastoma (N=3), pineoblastoma (N=1), and choroid plexus carcinoma (N=1). pVP shunt models included Aesculap Miethke proGAV (N=3), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 5), and Sophysa Polaris (N= 1). All 21 studies (100%) demonstrated ventriculo-thecal drug activity. 29% (6 of 21) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 21) of the studies had minimal peritoneal uptake (<12%), and 24% (5 of 21) demonstrated moderate peritoneal uptake (12–37%). pVP shunt models measuring minimal to no peritoneal uptake included: Aesculap Miethke proGAV (N=2), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 3), and Sophysa Polaris (N= 1). ConclusionsSuccessful drug delivery to the ventriculo-thecal space can be accomplished using pVP shunts: 80% of studies have minimal (<12%) peritoneal drug activity. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies reliably assess drug distribution.

Predictive value of standard serum markers for bone metastases in prostate cancer

BackgroundThe early detection of bone metastases is very important in prostate cancer follow-up. This study aimed to compare conventional tumor markers, namely free prostate-specific antigen (free PSA), total prostate-specific antigen (total PSA), free PSA/total PSA ratio, alkaline phosphatase (ALP) values, Gleason scores and 99 m Tc-MDP bone scintigraphy findings in the prediction of bone metastases in prostate cancer.MethodsIn total, 175 patients with prostate cancer who underwent whole-body bone scintigraphy were included in the study. All selected scintigraphic studies were reprocessed. Free PSA, total PSA, free PSA/total PSA ratio, alkaline phosphatase (ALP) values and Gleason scores of patients were recorded.ResultsThe results of our study show that the presence of bone metastasis correlates very weakly with free PSA/total PSA ratio (rho = 0.179), weakly with total PSA (rho = 0.318) and Gleason score (rho = 0.382), moderately with ALP (rho = 0.539), free PSA (0.416). Only ALP variable had a diagnostic value and ALP cutoff value was 76.50 IU/L, with 80% sensitivity and 82.1% specificity.ConclusionAccording to the results of our study; the free PSA, total PSA, free PSA/total PSA ratio and Gleason score values were not considered as a reliable parameter in the prostate cancer cases follow-up for bone metastasis development. Only ALP had a diagnostic value and ALP cutoff value was 76.50 IU / L with 80% sensitivity and 82.1% specificity in predicting bone metastases in prostate cancer.

Multi-input deep learning approach for Cardiovascular Disease diagnosis using Myocardial Perfusion Imaging and clinical data.

Accurate detection and treatment of Coronary Artery Disease is mainly based on invasive Coronary Angiography, which could be avoided provided that a robust, non-invasive detection methodology emerged. Despite the progress of computational systems, this remains a challenging issue. The present research investigates Machine Learning and Deep Learning methods in competing with the medical experts' diagnostic yield. Although the highly accurate detection of Coronary Artery Disease, even from the experts, is presently implausible, developing Artificial Intelligence models to compete with the human eye and expertise is the first step towards a state-of-the-art Computer-Aided Diagnostic system. A set of 566 patient samples is analysed. The dataset contains Polar Maps derived from scintigraphic Myocardial Perfusion Imaging studies, clinical data, and Coronary Angiography results. The latter is considered as reference standard. For the classification of the medical images, the InceptionV3 Convolutional Neural Network is employed, while, for the categorical and continuous features, Neural Networks and Random Forest classifier are proposed. The research suggests that an optimal strategy competing with the medical expert's accuracy involves a hybrid multi-input network composed of InceptionV3 and a Random Forest. This method matches the expert's accuracy, which is 79.15% in the particular dataset. Image classification using deep learning methods can cooperate with clinical data classification methods to enhance the robustness of the predicting model, aiming to compete with the medical expert's ability to identify Coronary Artery Disease subjects, from a large scale patient dataset.

Narrative review of practical aspects of aerosol delivery via high-flow nasal cannula.

Using high-flow nasal cannula (HFNC) as a "vehicle" to administer aerosolized medication has attracted clinicians' interest in recent years. In this paper, we summarize the current evidence to answer the common questions raised by clinicians about this new aerosol delivery route and best practices of administration. Benefits of trans-nasal aerosol delivery include increased comfort, ability to speak, eat, and drink for patients while meeting a range of oxygen requirements, particularly for those who need to inhale aerosolized medication for long periods. Aerosol administration via HFNC has been shown to be well tolerated by children and adults, with comparable or better delivery efficacy than other interfaces, ranging from 2-20%. In vitro and in vivo scintigraphy studies among pediatric and adult populations reported that the inhaled dose delivered via a vibrating mesh nebulizer is 2 to 3 fold greater than that via a jet nebulizer. For adults, placement of nebulizer at the inlet of humidifier increases inhaled dose while reducing rainout obstructing nasal prongs. When HFNC gas flow is set below patient inspiratory flow, aerosol deposition is higher than when the gas flow exceeds patient inspiratory flow; thus, if tolerated, titrating down HFNC gas flow during trans-nasal aerosol delivery, with close monitoring and the use of unit dose with high concentration are recommended. Trans-nasal pulmonary aerosol delivery has not been shown to increase bioaerosols generated by patients, but gas flow may disperse aerosols. Placement of a surgical or procedure mask over HFNC might reduce aerosol dispersion.

Apigenin-Loaded PLGA-DMSA Nanoparticles: A Novel Strategy to Treat Melanoma Lung Metastasis.

The flavone apigenin (APG), alone as well as in combination with other chemotherapeutic agents, is known to exhibit potential anticancer effects in various tumors and inhibit growth and metastasis of melanoma. However, the potential of apigenin nanoparticles (APG-NPs) to prevent lung colonization of malignant melanoma has not been well investigated. APG-loaded PLGA-NPs were surface-functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) for the treatment of melanoma lung metastasis. DMSA-conjugated APG-loaded NPs (DMSA-APG-NPs) administered by an oral route exhibited sustained APG release and showed considerable enhancement of plasma half-life, Cmax value, and bioavailability compared to APG-NPs both in plasma and the lungs. DMSA-conjugated APG-NPs showed comparably higher cellular internalization in B16F10 and A549 cell lines compared to that of plain NPs. Increased cytotoxicity was observed for DMSA-APG-NPs compared to APG-NPs in A549 cells. This difference between the two formulations was lower in B16F10 cells. Significant depolarization of mitochondrial transmembrane potential and an enhanced level of caspase activity were observed in B16F10 cells treated with DMSA-APG-NPs compared to APG-NPs as well. Western blot analysis of various proteins was performed to understand the mechanism of apoptosis as well as prevention of melanoma cell migration and invasion. DMSA conjugation substantially increased accumulation of DMSA-APG-NPs given by an intravenous route in the lungs compared to APG-NPs at 6 and 8 h. This was also corroborated by scintigraphic imaging studies with radiolabeled formulations administered by an intravenous route. Conjugation also allowed comparatively higher penetration as evident from an in vitro three-dimensional tumor spheroid model study. Finally, the potential therapeutic efficacy of the formulation was established in experimental B16F10 lung metastases, which suggested an improved bioavailability with enhanced antitumor and antimetastasis efficacy of DMSA-conjugated APG-NPs following oral administration.

Fabrication of a Thermosensitive In Situ Gel Nanoemulsion for Nose to Brain Delivery of Temozolomide

In this study, a thermosensitive in situ gel nanoemulsion was formulated by a low energy method for intranasal delivery of temozolomide to bypass the blood-brain barrier and optimize chemotherapy for glioblastoma. Various amounts of Labrasol, Transcutol®P, and Triacetin were chosen as nanoemulsion components based on the solubility and the partial pseudoternary phase diagrams studies. Poloxamer derivatives added to the selected nanoemulsion and gelling temperature optimized. The prepared in situ gel nanoemulsion containing temozolomide showed a mean droplet size of 16.25 ± 0.44 nm , a polydispersity index value of 0.35 ± 0.01 , and desirable pH and viscosity. In vitro release studies revealed that both nanoemulsion and in situ gel preparation have sustained release pattern in comparison to the control solution. Visual evaluation and droplet size and polydispersity index measurements showed both nanoemulsion and in situ gel nanoemulsion were stable during heating-cooling and freeze-thaw cycles and also centrifugation. Mucoadhesion percentage of in situ gel nanoemulsion was 37.037 ± 2.32 regarding ex vivo studies, which had a significant rise in comparison to control solution and nanoemulsion. Permeation across the nasal mucosa was 1.43- and 1.52-fold higher than the control solution for nanoemulsion and in situ nanoemulsion, respectively. Gamma scintigraphy study showed brain accumulation of developed nanoemulsion formulations. Our studies demonstrated optimized formulation has suitable physicochemical properties, desirable release profile, enhanced permeation across the nasal mucosa, and prolonged resistance time at the nasal mucosa. Therefore, in situ gel nanoemulsion would be an effective novel nasal delivery system for the treatment of glioblastoma.

Modified Reflux Scintigraphy Detects Pulmonary Microaspiration in Severe Gastro-Esophageal and Laryngopharyngeal Reflux Disease.

Previously described methodologies for detecting laryngopharyngeal reflux (LPR) have limitations. Symptoms alone are non-diagnostic, and pH-impedance studies have poor sensitivity. Pulmonary micro-aspiration is under-recognised in LPR and gastro-esophageal reflux disease (GERD). The present study aimed to describe the results of a modified technique for scintigraphic reflux studies in two groups with severe reflux: those with typical reflux symptoms and those with laryngopharyngeal manifestations of reflux. A prospective database of severely symptomatic, treatment-resistant reflux patients was grouped based upon predominant symptom profile of typical GERD or LPR. All patients underwent reflux scintigraphy. Results were obtained for early scintigraphic reflux contamination of the pharynx and proximal esophagus, and delayed contamination of the pharynx and lungs after 2h. 187 patients were studied (82 GERD, 105 LPR). The LPR patients were predominantly female (70.5% vs. 56.1%; p = 0.042) and older than the GERD group (median age 60years vs. 55.5years; p = 0.002). Early scintigraphic reflux was seen at the pharynx in 89.2% (GERD 87.7%, LPR 90.4%; p = 0.133), and at the proximal esophagus in 89.7% (GERD 88.9%, LPR 90.4%; p = 0.147). Delayed contamination of the pharynx was seen in 95.2% (GERD 93.9%, LPR 96.2%; p = 0.468). Delayed pulmonary aspiration was seen in 46% (GERD 36.6%, LPR 53.3%; p = 0.023). Reflux scintigraphy demonstrated a high rate of reflux-related pulmonary aspiration. Contamination of the proximal esophagus and pharynx was observed frequently in both groups of severe disease. The likelihood of pulmonary aspiration and potential pulmonary disease needs to be entertained in severe GERD and LPR.

Biodistribution of iron-oxide-stabilized 99mTc- ZrO2 nanoparticles in rabbit using honey as a capping agent—microwave-assisted sol–gel approach

One of the major biomedical problems facing worldwide is the diagnosis and treatment of tumor. This disease may lead to severe incidence with increased mortality rates. Therefore, it is the need of present era to develop advanced tools/methods for timely diagnosis of tumor. Aim of the present study is to evaluate the cytotoxicity and biodistribution of iron-oxide-stabilized zirconia (IOZH) nanoparticles with honey as a capping agent. In vivo-targeted diagnostic applications of stabilized ZrO2 nanoparticles are investigated through biodistribution of nanoparticles in rabbits. Nanoparticles (NPs) are synthesized using the microwave-assisted sol–gel method. Powers of microwave energy (100–900 W) are varied to synthesize stabilized zirconia NPs. Honey, as an organic capping agent, is added during synthesis. Structural results demonstrate the appearance of stabilized tetragonal phase of zirconia at 700 and 900 W without any further heat treatments. Smaller crystallite size of ~20 nm is observed for stabilized zirconia samples. Higher X-ray density is observed for pure tetragonal phase at 700 and 900 W. High dielectric constant (~55.8 at log f = 4) along with low tan loss is observed for zirconia prepared at 900 W. Magnetic results show superparamagnetic nature of the samples synthesized at 700 and 900 W. Radiolabeling along with biodistribution of iron-oxide-stabilized zirconia nanoparticles with technetium-99m is studied in normal rabbits. It is worth mentioning here that high-yield efficacy and stability along with its biodistribution and scintigraphy studies have been investigated. High uptake of radiotracer in bladder of rabbit is found to be potential candidate for its use in tumor therapies. Urination and physical properties of rabbit, after the post injection of nanoparticles, are checked periodically for many months and found normal.

How to deliver aerosolized medications through high flow nasal cannula safely and effectively in the era of COVID-19 and beyond: A narrative review

BackgroundThe treatments of COVID-19 involve some degree of uncertainty. Current evidence also shows mixed findings with regards to bioaerosol dispersion and airborne transmission of COVID-19 during high flow nasal cannula (HFNC) therapy. While coping with this global pandemic created hot debates on the use of HFNC, it is important to bring detached opinions and current evidence to the attention of health care professionals (HCPs) who may need to use HFNC in patients with COVID-19.AimThe purpose of this paper is to provide a framework on the selection, placement, and use of nebulizers as well as HFNC prongs, gas flow, and delivery technique via HFNC to help clinicians deliver aerosolized medications through HFNC safely and effectively in the era of COVID-19 and beyond.MethodsWe searched PubMed, Medline, CINAHL, and Science Direct to identify studies on aerosol drug delivery through HFNC using the following keywords: (“aerosols,” OR “nebulizers”) AND (“high flow nasal cannula” OR “high flow oxygen therapy” OR “HFNC”) AND (“COVID-19,” OR “SARS-CoV-2”). Twenty-eight articles including in vitro studies, randomized clinical trials, scintigraphy studies, review articles, prospective and retrospective research were included in this review.Discussion and resultsIt is not clear if the findings of the previous studies on bacterial contamination could be applied to viral transmission because they do not provide data that could be extrapolated to the risk of SARS-CoV-2 transmission. In the face of the unknown risk with the transmission of COVID-19 during HFNC therapy, the benefits of HFNC must be weighed against the risk of infection to HCPs and other patients. Due to the limited number of ventilators available in hospitals and the confirmed effectiveness of HFNC in treating hypoxemic respiratory failure, HFNC may prevent early intubation, and prolonged intensive care unit stays in patients with COVID-19.ConclusionClinicians should review the magnitude of this risk based on current evidence and use the suggested strategies of this paper for safe and effective delivery of aerosolized medications through HFNC in the era of COVID-19 and beyond.

Prognostic value of myocardial perfusion scintigraphy in diabetic patients and without coronary lesion

ObjectiveTo determine the prognostic value of myocardial perfusion scintigraphy-gated SPECT in patients with diabetes mellitus and without obstructive coronary artery disease. Materials and methodsThis retrospective study included consecutive patients undergoing adenosine stress-rest myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin between 2009 and 2011. The patients had diabetes mellitus and coronary angiography without significant coronary lesions. In total, 37 diabetic patients (female/male: 20/17; mean age: 65.2 (range: 40−78). 29 non-diabetic patients were included wich are matched with the group of diabetic patients with positive MPI. The group of non-diabetic patients had scintigraphy with myocardial ischemia and without angiographic lesions. A 36-month clinical follow-up was performed, and major cardiac events were recorded. ResultsIn 78.3% (29/37) of diabetic patients the scintigraphic study showed myocardial ischemia, while it was negative in the 21.7%. The cardiac event rate in both groups was 6%. In diabetics with a myocardial perfusion study with myocardial ischemia, there were 3 major cardiac events. In diabetic patients with negative study had no cardiac event. In the non-diabetic control group the cardiac events rate was 3.4% (1/29). ConclusionIn diabetic patients without obstructive coronary disease, myocardial perfusion study can be predictor of cardiac events. A negative study can be an indicator of a better cardiovascular prognosis.

Comparative Analysis of Collagen and Chitosan-based Dressing for Haemostatic and Wound Healing Application

Collagen and chitosan have haemostatic, tissue fix and wound healing properties but the poor mechanical property limits their application. Therefore, various concentrations of collagen (1-6%) and chitosan (1-2%) were used to develop biopolymer-coated gauzes, with and without glycerol as plasticiser. Glycerol-treated gauzes showed desired mechanical and adhesive property in comparison to polymer-coated gauzes alone. Developed gauzes were characterized using differential scanning calorimetry, thermal gravimetric analysis and Fourier transform infrared spectrophotometry to confirm the biopolymer coating and stability. Scanning electron microscopy showed multilayer coating of the biopolymer and faster clotting in chitosan gauzes in comparison to collagen. Surface plasmon resonance assay confirmed that chitosan exhibited more binding affinity of 65 RU in comparison to collagen, which showed 55 RU with erythrocytes. Decrease in the value of plateletcrit and mean platelet volume confirmed platelet adhesion and aggregation over the surface of polymer-coated dressings. Gamma scintigraphy studies showed 85 ± 2% formulation retention up to 12h at the wound site in comparison to 40 ± 3% retention of the radiopharmaceutical alone. Collagen and chitosan-coated gauze showed 226 ± 15s and 179 ± 12s haemostasis time, respectively, which was significantly less from 506 ± 15s in standard gauze. Chitosan gauze showed faster wound healing in comparison to the collagen-coated gauze. Chitosan and collagen-coated gauzes showed 55 ± 4% wound contraction on day seven in comparison to 25 ± 2% in the control group, while chitosan gauzes showed complete wound contraction on day fourteenth, while the collagen-coated gauze showed 90 ± 3% on the same day.

A new diagnostic paradigm for laryngopharyngeal reflux disease: correlation of impedance-pH monitoring and digital reflux scintigraphy results.

No gold-standard investigation exists for laryngopharyngeal reflux (LPR). Multichannel intraluminal impedance (MII)-pH testing has uncertain utility in LPR. Meanwhile, reflux scintigraphy allows immediate and delayed visualisation of tracer reflux in the esophagus, pharynx, and lungs. The present study aimed to correlate MII-pH and scintigraphic reflux results in patients with primary LPR. Consecutive patients with LPR underwent MII-pH and scintigraphic reflux studies. Abnormal values for MII-pH results were defined from existing literature. MII-pH and scintigraphic data were correlated. 105 patients with LPR [31 males (29.5%), median age 60years (range 20-87)] were studied. Immediate scintigraphic reflux was seen in the pharynx in 94 (90.4%), and in the proximal esophagus in 94 (90.4%). Delayed scintigraphic contamination of the pharynx was seen in 101 patients (96.2%) and in the lungs of 56 patients (53.3%). For MII-pH, abnormally frequent reflux was seen in the distal esophagus in 12.4%, proximal esophagus in 25.7%, and in the pharynx in 82.9%. Patients with poor scintigraphic clearance had higher Demeester scores (p = 0.043), more proximal reflux episodes (p = 0.046), more distal acid reflux episodes (p = 0.023), and more prolonged bolus clearance times (p = 0.002). Reflux scintigraphy has a high yield in LPR patients. Scintigraphic time-activity curves correlated with validated MII-pH results. A high rate of pulmonary microaspiration was found in LPR patients. This study demonstrated a high level of pharyngeal contamination by scintigraphy and MII-pH, which supports the use of digital reflux scintigraphy in diagnosing LPR.

Intranasal solid lipid nanoparticles for management of pain: A full factorial design approach, characterization & Gamma Scintigraphy

Pain is a noxious stimulus caused due to tissue damage and varies from mild to severe. Nalbuphine (NLB) is an approved, inexpensive, non-controlled, opioid agonist/antagonist analgesic used worldwide in various clinical settings for pain management. The current study aims to formulate NLB loaded solid lipid nanoparticles (SLNs) using solvent injection technology. The morphological and chemical structure of the developed SLNs were characterized using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM) and Fourier Transformation Infrared Spectroscopy (FTIR). The results revealed from the point prediction confirmation in design expert software was the formulation of NLB-SLNs with an average particle size of (170.07 ± 25.1 nm), encapsulation efficiency (93.6 ± 1.5%) & loading capacity of 26.67%. The in-vitro permeation of developed NLB-SLNs was observed to be 94.18% at 8 h when compared with NLB solution whose maximum permeation was seen within 3 h of application. Efficacy of the formulation was also evaluated using eddy's hot plate method, where the onset of action started within 10 min of administration, and the maximum effect was observed at 1 h. The NLB-SLNs was screened for cytotoxicity in human embryonic kidney cells (HEK-293), and the dosage was considered safe when administered intranasally in animal since no detectable effect to the brain was observed. Biodistribution and gamma scintigraphy study of NLB-SLNs showed the prepared formulation reaching the target site, i.e. brain and was retained. Conclusively, the prepared NLB-SLNs formulation was safe and effective in producing an analgesic effect in vivo.

Real-time intraoperative functioning lumen imaging probe during endoscopic per-oral pyloromyotomy (pop)

BackgroundEndoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent of the pyloromyotomy continues to present a challenge as there are no standardized tools for measuring changes in pyloric distensibility during the procedure. The objective of this study was to evaluate the utility of using impedance planimetry with endoscopic functional luminal imaging probe (FLIP) to measure changes in pyloric distensibility after POP, and to compare these changes with improvement in symptoms and objective gastric emptying.MethodsPatients with medically refractory gastroparesis underwent POP with FLIP measurements of the pylorus (EndoFLIP®, Medtronic, Fridley MN). FLIP measurements, as well as changes in symptoms measured by the validated gastroparesis cardinal symptom index (GCSI) and scintigraphic gastric emptying studies (GES), were evaluated before and after POP.ResultsA total of 14 patients underwent measurement with FLIP during POP, 12 of whom had pre- and post-POP measurements. Mean pyloric diameter increased by 1.4 mm, from 13.9 mm to 15.3 mm (p = 0.0012). Mean distensibility index increased from 6.2 mm2/mmHg to 9.1 mm2/mmHg (p = 0.0074). Successful division of the pylorus was achieved in 100% of patients with a mean operative time of 36 min and no perioperative complications. The mean length of stay was 0.7 days (0–3 days). Post-POP mean GCSI score improved from 2.97 to 2.28 at a mean follow-up time of 27 days (p < 0.001). Objective improvement in gastric emptying was observed in 80% of patients with scintigraphic GES, with mean four-hour retention decreasing from 46.3% to 32.4% (p < 0.007).ConclusionsFLIP is a safe and feasible tool to provide objective measurements during POP. Larger cohorts with longer follow-up are required to determine if measured improvements in pyloric diameter and distensibility are predictive of sustained improvements in GCSI and GES.

Comparative evaluation of intranasally delivered quetiapine loaded mucoadhesive microemulsion and polymeric nanoparticles for brain targeting: pharmacokinetic and gamma scintigraphy studies

BackgroundTreatment in neurological disorders like schizophrenia requires continuous presence of drug in the brain for a prolonged period of time to achieve an effective therapeutic response. Delivery of antipsychotic drug quetiapine in the form of conventional delivery systems suffers from low oral bioavailability, first-pass metabolism, and frequent dosing. In addition to that biological obstacles present at the brain interface also hinders the transport of quetiapine across the brain. In the present study, nasal delivery of quetiapine loaded nanoparticles and microemulsion formulation were designed to evaluate their individual in vivo potential to achieve brain targeting. Chitosan-based polymeric nanoparticles and mucoadhesive microemulsion systems were developed through ionic gelation and water titration method respectively.ResultsMicroemulsion showed globule size lower than 50 nm with 95% drug loading while, nanoparticles exhibited 65% drug loading with particle size of 131 nm. Nasal diffusion study showed highest diffusion with chitosan-based mucoadhesive microemulsion over nanoparticles suggesting permeation-enhancing effects of chitosan. Due to the overall hydrophilic nature, quetiapine-loaded nanoparticles could not diffuse superiorly across nasal mucosa, hence, showed 1.3 times lesser diffusion compared to mucoadhesive microemulsion. Pharmacokinetics in rats showed highest brain concentration and 1.9-folds higher nasal bioavailability with mucoadhesive microemulsion over nanoparticles suggesting direct brain transport through olfactory route bypassing blood-brain barrier.ConclusionHigher quetiapine transport with mucoadhesive microemulsion suggested that synergistic effects like tight junction modulation by chitosan and unique composition facilitating smaller globule size could be responsible for higher brain transport. Imaging study by gamma scintigraphy also supported pharmacokinetic outcomes and concluded that mucoadhesive microemulsion could be a promising nanocarrier approach for non-invasive nose to brain delivery.Graphical abstract

Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential −16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.

MULTIMODAL LOGIT MODEL FOR PREDICTING THE EFFICIENCY OF MYOCARDIAL REVASCULARIZATION BY THE METHOD OF CORONARY ARTERY BYPASS GRAFTING IN PATIENTS WITH CORONARY HEART DISEASE.

building of a mathematical logit model for possible prediction of the outcome of surgical treatment bythe method of coronary artery bypass grafting (CABG) in patients of different groups with coronary heart disease(CHD) based on myocardial viability (MV) assessment. To implement the set clinical tasks, 62 patients with coronary heart disease with preservedsystolic function and systolic dysfunction were examined. The mean age of the subjects was (59.6 ± 8.2) years. 35(56 %) patients had a variant of heart failure (HF) with an ejection fraction (EF) of 45 % or less. 27 (44 %) patientshad EF of 46 % or more. 5 (8.0 %) patients denied myocardial infarction (MI). Myocardial scintigraphy (MSG) wasperformed on Infinia Hawkeye combined gamma-camera (GE, USA) with integrated CT. The studies were performedin SPECT and SPECT / CT with ECG synchronization (Gated SPECT) modes. 99mTc-MIBI with an activity of 555-740 MBqwas used. MSG was performed in the dynamics of treatment (before CABG and after CABG) according to One Day Restprotocol. A total of 124 scintigraphic studies were performed. Samples of patients studied «before» and «after» the treatment were compared using nonparametricWilcoxon test (Wilcoxon Matched Pairs Test). A multivariate regression model, that reflects a statistically significanteffect on the treatment response (MV after treatment) of such cardiac activity indicators as LV EF (%), coronary bedlesion area and MV level (%) before treatment, was built. The above-described regression relationship between thethree above-defined functional factors of cardiac activity before treatment and the therapeutic effect in the formof the change in MV can be construed as a diagnostic model that predicts the treatment outcome. This scientific study allows to build logit models to predict the expected outcome of coronary heartdisease surgical treatment in patients of different groups. The presented multivariate regression model is characterised by a sufficiently high for biostatistical studies adjusted coefficient of determination (Adjusted R2 = 0,893 (F = 173,4; p < 0,001)).

Hepatobiliary Scintigraphy to Evaluate Biliary Complications of Pediatric Liver Transplantation: An Account of an Experience

Hepatobiliary scintigraphy (HS) is a noninvasive imaging technique whose use in the follow-up of liver transplantation has not been duly documented. The main objective of this study is to describe the experience of using this technique to detect biliary complications in pediatric patients following liver transplantation. A retrospective, observational, and descriptive study involving 86 pediatric patients who had undergone liver transplantation between 2013 and 2018. Of the 86, 31 had undergone at least one HS during their postoperative period. A total of 45 studies were performed on 31 patients (36% of the patients undergoing transplantation during that time period). Patient ages ranged from 5 to 204 months (mean = 50 months). A total of 22 transplants (71%) were from living donors and 9 (29%) were from cadaveric donors. Of the 45 studies, 22 were positive for biliary complications, and all of them had an impact on clinical decision-making. The remaining 23 studies were negative. Of these 23, 19 continued under medical treatment and the other four underwent an additional intervention with positive surgical outcomes in all cases. All scintigraphy studies revealed hepatocellular dysfunction and cholestasis. The HS is a useful, noninvasive, and diagnostic procedure for the early diagnosis of biliary complications that may impact the evolution of disease in liver transplant patients. It allows the treating physician to make a more informed decision regarding expectant management, surgical management, or a less invasive course of action for transplantation complications.

Development of Cinnarizine Microballoons by Sequential Optimization and In Vivo Imaging by Gamma Scintigraphy

Background: The drug cinnarizine is used in the treatment of vertigo and migraine. The main drawback is its very low water solubility which causes unpredictable bioavailability. Solubility is better in acidic pH. Therefore, gastro-retentive formulation would be beneficial to improve the bioavailability of the drug. Objective: The objective of the study was to prepare floating microballoons of cinnarizine which would float in the gastric fluid and release the drug in a sustained manner. Methods: Microballoons were prepared by diffusion solvent evaporation technique using polymers (Eudragit® S100, Eudragit® RLPO, Eudragit RL®100), characterised by FTIR, XRD, DSC and optimized by sequential simplex design. For optimization, formulations were graded with respect to formulation efficiency (percentages of yield, sphericity and drug content) and performance index (buoyancy and dissolution efficiency), from which the overall response of the formulations was determined. Finally, the optimized formulation was radiolabelled with 99mTc-MIBI and fed to Wistar albino rats and was evaluated for gastric retention by gamma scintigraphic study. Results: FTIR studies indicated drug and polymers were compatible. DSC and XRD analysis confirmed that the drug was in amorphous state in the formulation. SEM studies confirmed the sphericity of the microballoons. Formulation N7 showed the best overall response (65.61) which was the nearest to the target. Gamma scintigraphic study confirmed that the formulation was retained in the stomach for more than 5 h. Conclusion: The results indicated that floating microballoons of cinnarizine would stay in the stomach for prolonged period and thereby improve the bioavailability of the drug.

A transformational change in scintigraphic gastroesophageal reflux studies: A comparison with historic techniques.

The inclusion of scintigraphy in the diagnostic algorithm for gastroesophageal reflux is controversial due to variability in methodology and reporting. A novel scintigraphic reflux study has been developed and validated against the current standards for the diagnosis of gastroesophageal reflux disease (GORD). To compare a new scintigraphic reflux test against historic techniques and standardised diagnostic reference tests for gastroesophageal reflux disease. Paired scintigraphic studies were conducted in seventeen patients. All patients underwent at least one other standardised diagnostic reflux test such as 24- hour oesophageal impedance/ pH, and oesophageal manometry, barium swallow, gastroscopy or the Peptest. Patients inadvertently presented at sites B for scintigraphic reflux testing rather than at Site A which was part of an approved study. The findings from sites B did not correlate with clinical symptoms and other diagnostic reference tests from GORD. These studies were then repeated at Site A with approval from the patients. A second reflux study was performed at site A, utilising a novel technique with the capability of assessing oesophageal and extra-oesophageal disease. The Site A technique shows good concordance with the reference diagnostic tests with an accuracy of 82.4% and kappa of 0.64 (SE: 0.16, p = 0.00). Site B had an overall accuracy of 47.1% and kappa of 0.066 (SE: 0.068, p = 0.45). The Site A technique shows higher accuracy than either site B or the historic reflux techniques. It has characteristics that make it an effective screening tool for assessment of local oesophageal disease and its extraoesophageal manifestations.