The efficacy of ultrasound-guided upper thoracic erector spinae plane block for postoperative analgesia in proximal shoulder surgery and its effect on phrenic nerve function: A prospective exploratory study.

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.

Investigation of the Potential of Nanoparticles as a New Drug Delivery System for Endodontic Treatment: An In Vitro Study.

Background: Endodontic treatment involves the removal of infected dental pulp and subsequent disinfection of the root canal system. The effectiveness of drug delivery systems in root canal disinfection is critical for successful treatment outcomes. This in vitro study explores the potential of nanoparticles as a novel drug delivery system for endodontic treatment. Materials and Methods: Nanoparticles were synthesized using a biocompatible polymer and loaded with an antimicrobial agent. A total of 60 extracted human teeth were prepared to create standardized root canal infections. The teeth were randomly divided into three experimental groups: (1) conventional irrigation, (2) nanoparticle irrigation, and (3) control (no irrigation). The root canals in each group were irrigated with their respective solutions for 5 minutes. After treatment, microbial samples were collected from the root canals and cultured for colony-forming unit (CFU) analysis. The depth of penetration of nanoparticles into dentinal tubules was assessed using scanning electron microscopy (SEM). Results: The conventional irrigation group showed a reduction in microbial load from an average of 7.8 × 10^5 CFU/mL (SD ± 1.2 × 10^5) to 3.4 × 10^4 CFU/mL (SD ± 7.9 × 10^3) (P < 0.001). In contrast, the nanoparticle irrigation group exhibited a more significant reduction, with a decrease in CFU to 1.2 × 10^3 CFU/mL (SD ± 4.2 × 10^2) (P < 0.001). SEM analysis revealed deep penetration of nanoparticles into dentinal tubules, reaching an average depth of 150 µm. Conclusion: Nanoparticles loaded with antimicrobial agents demonstrated superior efficacy in reducing microbial load within root canals compared to conventional irrigation. Their ability to penetrate dentinal tubules suggests their potential as an innovative drug delivery system for endodontic treatment. Further research and clinical trials are warranted to validate these promising in vitro results and assess the safety and efficacy of nanoparticles in clinical practice.

A Novel Nephropsychology Clinic: Partnering With Patients in the Era of Value-Based Care in Nephrology.

CKD and end-stage kidney disease are highly prevalent and complex chronic conditions with a high disease burden that corresponds to a high cost of care. Mental health conditions have a high prevalence in this population and add to the burden of disease, increase the cost of care, and are co-related with worse clinical outcomes. Despite these clear co-relations, mental health disorders remain underdiagnosed and undertreated in this population, secondary to multiple reasons, including patient-specific factors as well as systematic issues, including difficulty in accessing mental health experts. Here we describe a novel collaborative care model for patients with advanced CKD within the nephrology clinic space, in the form of a nephropsychology clinic. We present the details of our clinic, our preliminary findings, and propose that an integrated behavioral health model offers convenience for the patient and improves workflow for the physician, allowing a pathway to timely mental health interventions.

Revisiting the significance of nano-vitamin D for food fortification and therapeutic application.

OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.

Is There a Role for Alcohol Septal Ablation in Young Patients with Medically Refractory Hypertrophic Obstructive Cardiomyopathy?

Surgical myectomy is recommended for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) after optimal pharmacological therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) is reserved for high-risk adults. Symptomatic patients below 25 years underwent either surgery or PTSMA after heart-team discussion and informed consent. Echocardiography assessed gradients in surgical group. PTSMA group underwent invasive transseptal hemodynamic assessment, selective coronary angiography and super-selective cannulation of septal perforators using microcatheters. Contrast echocardiography through the microcatheter identified the myocardial target for PTSMA. Hemodynamic and electrocardiographic monitoring guided alcohol injection. Both groups were continued on beta-blockers. Symptoms, echocardiographic gradients and Brain natriuretic peptide (NTproBNP) measurements were assessed on follow-up. Twelve patients aged 5-23 years (11-98 kg) formed the study group. Indications for PTSMA in 8 patients included abnormal mitral valve anatomy warranting replacement (n = 3), Jehovah's witness (n = 2), severe neurodevelopmental and growth retardation (n = 1) and refusal of surgery (n = 2). PTSMA targeted first perforator (n = 5), second perforator (n = 2) and anomalous septal artery from left main trunk (n = 1). Outflow gradient reduced from 92.5 ± 19.7 to 33.1 ± 13.5 mmHg. At a median follow-up of 38 months (range 3-120 weeks), the peak instantaneous echocardiographic gradient was 32 ± 16.5 mmHg. Gradient reduced in four surgical patients from 86.5 ± 16.3 mmHg to 42 ± 14.7 mm Hg. All patients were in NYHA class I/II on follow-up. The mean NTproBNP in PTSMA group reduced from 6084 ± 3628 pg/ml to 3081 ± 2019 pg/ml; it was 1396 and 1795 pg/ml in surgery. PTSMA may be considered in medically refractory high-risk young patients. It relieves symptoms and reduces gradient. Though surgery is preferred in young patients, PTSMA may have a role in selected patients.

Retrospective Evaluation of Moderate Sedation Visits That Used Oral Meperidine and Hydroxyzine With Oral or Intranasal Midazolam.

Purpose: To examine the influence of substituting intranasal (IN) midazolam (MID) for oral (PO) MID, within the three-drug combination of meperidine (MEP), hydroxyzine (H) and MID, on sedation treatment outcomes. Methods: A retrospective, cross-sectional analysis examined patient variables and sedation outcomes in 508 pediatric dental patients sedated by single- and multi-drug sedation regimens (MEP-H; MEP-H-(PO)-MID; MEP-H-(IN)-MID; single-agent MID). The outcome assessment examined sedation visit effectiveness, sedation treatment completion, treatment time and medication administration to discharge time. Multivariable logistic regression analyses assessed predictive variables associated with sedation visit effectiveness. Results: Both three-drug combinations (MEP-H-(PO)-MID; MEP-H-(IN)-MID) were used for behavior guidance in children of a similar age (median age=7.1 and 6.5 years, respectively, for the two drug combinations) and weight (median weight = 23.7 and 23.5 kg, respectively, for the two drug combinations). These three-drug combinations had a higher likelihood of sedation effectiveness over the reference sedation regimen of single-agent midazolam (MEP-H-(PO)-MID adjusted odds ratio [OR] = 2.65; 95 percent confidence interval [95% CI]=1.09 to 6.45; P=0.032; and MEP-H-(IN)-MID OR=2.08; 95% CI=1.03 to 4.18; P=0.039). MEP-H-(IN)MID was associated with a shorter medication administration to discharge time for patients by 23 minutes (interquartile range [IQR]=9.5 to 34 minutes) compared to MEP-H-(PO) MID (P<0.05) while providing a comparable number of teeth treated (median=five). All sedation drug regimens, including MEP-H-(IN)MID, had high levels of oxygen saturation during all sedation appointments. Conclusion: Substituting IN for PO MID in MEP-H-MID was associated with a shorter total time to discharge while demonstrating comparable efficacy during sedation.

Preoperative Diffusion Tensor Imaging in Supratentorial Intra-Axial Brain Tumors: Its Role in Predicting Tumor Histology and Prognosis as well in Surgical Planning and Resection.

Objective There are a large number of prospective studies that use diffusion tensor imaging (DTI) to show the relationship between intracranial tumors and white matter (WM) fibers. We studied the role of DTI in supratentorial intra-axial (ST-IA) tumors of the brain in deciding the surgical approach with maximal resection and minimal or no deficit and in predicting the histological characterization of the tumor and the neurological outcome. Methods A total of 91 cases of ST-IA tumors were included in our study. The neurological status of the patients was assessed preoperatively, and the tumor volume and DTI pattern were noted radiologically. Surgical plan was decided by the senior consultants of the neurosurgery department taking into consideration the findings of tractography and magnetic resonance imaging. The neurological status and the extent of resection were evaluated postoperatively, and the correlation between histopathology with DTI was studied. Results Of the 91 patients, 25 had high-grade glioma (HGG), 60 had low-grade glioma (LGG), and 6 were metastatic lesions. Gross total excisions were done mostly in patients with DTI showing displaced fibers and subtotal/partial resections were done mostly in disrupted/infiltrated tracts, which was statistically significant. The correlation between histopathology and tractography revealed that intact/displaced tracts were seen mostly in LGG (79%), whereas 86% of HGG showed disrupted/infiltrated fibers; both were statistically significant. Conclusion Preoperative DTI in ST-IA brain tumors is an important tool for deciding the appropriate surgical approach for maximal safe resection, thus improving the post-op neurological outcome in patients. It also helps in predicting the tumor histology while also serving as an important prognostication indicator.

Design and Development of a Topical Nanogel Formulation Comprising of a Unani Medicinal Agent for the Management of Pain.

The oil of the Unani medicinal herb Baboona (Matricaria chamomilla) has shown potential in the management of pain. However, predicaments such as poor skin penetration, skin sensitization, liable to degradation, and volatile nature restrict its use. Therefore, our group for the first time has developed a carrier-based delivery system to facilitate the direct application of chamomile oil to the forehead. The developed nanogel was characterized for physical parameters such as compatibility, TEM, and stability studies. Further, it was also evaluated for pH, viscosity, spread ability, and extrudability, as well as through texture analyses, in vitro studies, and skin irritation tests. The formulation was successfully developed with all the necessary attributes. The in vitro studies revealed the enhanced skin penetration of chamomile oil nanogel. The in vivo studies were also performed in chemically induced pain models, mimicking migraine. The studies show significant improvement of the pain threshold for chamomile nanogel when compared to the positive control group and the results were comparable to marketed diclofenac formulations. Finally, the encapsulation into nanogel reduced the skin irritation property. The nanogel formulation showed promising effects in the pain management of migraine.

Role of Preoperative Oral Rehydration Solution on Myocardial Ischaemia During Orthopaedic Surgery under Spinal Anaesthesia: A Prospective Randomised Study.

Objective: Preoperative oral rehydration solution (ORS) supplementation offers wide postoperative benefits, but its role in reducing post-spinal myocardial ischaemia is uncertain. We evaluated this aspect in elective lower limb orthopaedic surgeries and compared it to conventional preoperative fasting. Methods: Prospectively, we randomised 126 patients aged >60 years into two groups: (A) received reconstituted ORS (1000 mL) during the overnight preoperative fasting, continued up to 2 hrs prior to spinal anaesthesia (SA) induction; (B) kept on conventional overnight preoperative fasting. This study evaluated electrocardiographic ischaemic changes at 2, 5, 10, 15, and 30 minutes after SA induction. Results: In total, 27 patients (group A: 7; group B: 20) developed transient electrocardiographic ischaemic changes. On intergroup comparison, group B had a significantly higher incidence at all time points, with highest statistical levels at 5- and 10-minutes ((P < 0.001). The receiver operating characteristic curve at a threshold fasting duration (fluids) of >3 hours, had an area-under-curve of 0.74 to predict such changes within 30 minutes of SA induction (sensitivity 96.30%, specificity 55.56%, accuracy 64.29%, odds ratio 32.50, relative risk 20.80, (P < 0.001). Post-spinal hemodynamic changes were higher in group B than in A; hypotension and tachycardia were statistically significant ((P=0.020). The pleth variability index was significantly higher ((P < 0.001), while perfusion index was significantly lower (P < 0.001) in group B at all time points. Conclusion: Preoperative ORS supplementation significantly reduced post-spinal transient ischaemic electrocardiographic changes in elderly patients than conventional overnight fasting.

Reduction in postoperative sore throat by preoperative nebulization with dexmedetomidine, ketamine or saline: A prospective, randomized-controlled trial.

Background and Aims: Postoperative sore throat (POST) is a minor but distressing complication following general anesthesia. The current literature on the effect of preoperative nebulization with dexmedetomidine, or ketamine on POST is, however, sparse. So, we compared the effect of preoperative nebulization with these drugs on POST. Material and Methods: One hundred and thirty-two American Society of Anaesthesiology (ASA) grade I-II patients undergoing elective laparoscopic surgeries under general anesthesia were randomized into three equal groups: D, K, or C to receive dexmedetomidine, ketamine, or saline as preoperative nebulization, respectively. The primary objective was to compare the incidence and severity of POST, as inferred from the patient interviews at 2, 6, 12, 24-h postoperatively. Results: Group D had a significantly lower incidence (29.5%) and severity (12: mild; 1: moderate) of POST compared to group K (54.5% [21: mild; 3: moderate]) and group C (56.8% [19: mild; 6: moderate]), at 2-h postoperatively. The same trend was observed at 6-h postoperatively (group D: 22.7% [9: mild; 1: moderate]); group K: (40.9% [17: mild; 1: moderate]); group C (50% [17: mild; 5: moderate]). The mean arterial pressure was significantly lower in group D at 15 min intraoperatively (84.09 mmHg, P = 0.018) and immediate postoperatively (97.60 mmHg, P = 0.034). The postoperative sedation, nausea, and vomiting was not statistically significant. Conclusion: Preoperative nebulization with dexmedetomidine is effective in the reduction of the incidence and severity of early POST.

Intranasal inorganic cerium oxide nanoparticles ameliorate oxidative stress induced motor manifestations in haloperidol-induced parkinsonism.

Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated neurological diseases. However, oral and intravenous administration of CONPs is limited due to their poor physicochemical characteristics, low bioavailability, rapid systemic clearance, poor blood-brain penetration and dose-dependent toxicity. To overcome these challenges, we developed intranasal CONPs and evaluated their potential in the experimental PD model. CONPs were prepared by homogenous precipitation using tween 80 as a stabilizer and methanol/water as solvent. The optimization was done using Central Composite Design (CCD). The CONPs synthesis was confirmed by UV and FTIR. The optimized CONPs were small-sized (105.1 ± 5.78 nm), spherical (TEM), uniform (PDI, 0.119 ± 0.006) and stable (ZP, -22.7 ± 1.02 mV). Energy-dispersive X-ray analysis showed characteristic signals of Ce in developed CONPs. The X-ray diffraction pattern described the cubic fluorite structure and nano-crystalline nature of CONPs. The CONP anti-oxidant activity was found to be 93.60 ± 0.32% at 25 µg/mL concentration. Finally, motor manifestation studies like the forced swim test, locomotor test, akinesia, catalepsy, and muscle coordination test were conducted to assess the motor dysfunctions and behavioral activity in all four animal groups. Results of the in vivo motor manifestation studies in the haloperidol-induced PD rat model showed that co-administration of intranasal CONPs along with a half dose of levodopa resulted in significant protection, and results were significantly different from the untreated group but not significantly different from the healthy group. In conclusion, intranasal CONPs can be useful in ameliorating oxidative stress through their antioxidant effect and could be prospective therapeutics for the treatment of motor manifestations in Parkinson's disease.

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats.

Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson's disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration. Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model. Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 µg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein). Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.

Development and Antibacterial Investigation of Linezolid-Loaded SPIONs and HPLC Method Development for Quantitative Analysis of Linezolid.

BACKGROUND: Linezolid (LNZ) is extremely prone to resistance. The development of resistance to LNZ should be taken into consideration when selecting this drug as a therapeutic option. It is well established that reactive oxygen species (ROS) generated by iron oxide nanoparticles (MNPs) could kill the infecting bacteria. So, we hypothesized the synergistic antibacterial effect of iron oxide nanoparticles and LNZ. OBJECTIVE: To study the release and antibacterial effects of LNZ-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on Staphylococcus aureus and Streptococcus pneumoniae. METHOD: Ferrofluid containing SPIONs was synthesized via chemical co-precipitation method and stabilized by sodium lauryl sulphate (SLS). SPIONs were then loaded with LNZ and characterized for particle size, FT-IR, XRD, and entrapment efficiency. Further antibacterial activity of SPIONs and LNZ-loaded SPIONs was investigated. For the in vitro release findings, HPLC analytical method development and validation were performed. RESULTS: Isolation of LNZ was accomplished on a C-18 column with methanol-TBHS (tetra butyl ammonium hydrogen sulphate, 50:50, v/v). The eluate was monitored at 247 nm with a retention time of 4.175 min. The MNP's DLS measurement revealed monodispersed particles with an average size of 16.81 ± 1.07 nm and PDI 0.176 ± 0.012. In optimized formulation, 25 ± 1.75% (w/w) of the drug was found to be entrapped. XRD revealed uniform coating of oleic acid covering the entire magnetic particles' surface with no change in its crystallinity. An effective antimicrobial activity was observed at the lowered dose of drug. CONCLUSIONS: A robust HPLC method was developed to quantify the LNZ in MNPs, and outcomes showed that the reduced dose of LNZ incorporated in SPIONs was able to show similar activity as the marketed product. HIGHLIGHTS: Successfully reduction of the dose of LNZ was established with the aid of biocompatible MNPs to attain the equivalent antibacterial activity.

Advanced multifunctional nano-lipid carrier loaded gel for targeted delivery of 5-flurouracil and cannabidiol against non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.

Experience with the largest custom-made 48 mm fenestrated atrial septal occluder device and its 4-year follow-up.

Atrial septal defects (ASDs) measuring <38 mm are referred for transcatheter closure. Availability of larger devices up to 46 mm extended the inclusion criteria. An elderly hypertensive male with a 44 mm secundum ASD and coexistent sick sinus syndrome and atrioventricular (AV) nodal block presented with syncope. Balloon interrogation unmasked restrictive left ventricular (LV) physiology. After AV synchronous pacing, balloon-assisted deployment of a custom fenestrated 48 mm Figulla septal occluder (Occlutech Inc., Schaffhausen, Switzerland) prevented a rise of LV end-diastolic pressures beyond 12 mmHg. Echocardiogram and computed tomography after 4 years confirmed a patent fenestration and favorable remodeling. This report of the clinical use of the largest ASD device demonstrated the feasibility of closure of extremely large defects despite a restrictive LV.

Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation.

Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely 99mTc-Sulfur colloid (SC), 99mTc-Phytate (Phy) and 99mTc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29-1.48 MBq in 100 µl normal saline) of either 99mTc-Phy/ 99mTc-SC/ 99mTc-HSA into the tail as 'mock-venom'. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% w/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. 99mTc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of 99mTc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (P < 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, 99mTc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to 99mTc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that 99mTc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a significant reduction in the need for sacrificing large number of animals, particularly during initial screening phase of drug development cycle.

Evaluating diaphragmatic dysfunction and predicting non-invasive ventilation failure in acute exacerbation of chronic obstructive pulmonary disease in India.

BACKGROUND: Baseline diaphragmatic dysfunction (DD) at the initiation of non-invasive ventilation (NIV) correlates positively with subsequent intubation. We investigated the utility of DD detected 2 hours after NIV initiation in estimating NIV failure in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. METHODS: In a prospective-cohort design, we enrolled 60 consecutive patients with AECOPD initiated on NIV at intensive care unit admission, and NIV failure events were noted. The DD was assessed at baseline (T1 timepoint) and 2 hours after initiating NIV (T2 timepoint). We defined DD as ultrasound-assessed change in diaphragmatic thickness (ΔTDI) <20% (predefined criteria [PC]) or its cut-off that predicts NIV failure (calculated criteria [CC]) at both timepoints. A predictive-regression analysis was reported. RESULTS: In total, 32 patients developed NIV failure, nine within 2 hours of NIV and remaining in next 6 days. The ∆TDI cut-off that predicted NIV failure (DD-CC) at T1 was ≤19.04% (area under the curve [AUC], 0.73; sensitivity, 50%; specificity, 85.71%; accuracy; 66.67%), while that at T2 was ≤35.3% (AUC, 0.75; sensitivity, 95.65%; specificity, 57.14%; accuracy, 74.51%; hazard ratio, 19.55). The NIV failure rate was 35.1% in those with normal diaphragmatic function by PC (T2) versus 5.9% by CC (T2). The odds ratio for NIV failure with DD criteria ≤35.3 and <20 at T2 was 29.33 and 4.61, while that for ≤19.04 and <20 at T1 was 6, respectively. CONCLUSIONS: The DD criterion of ≤35.3 (T2) had a better diagnostic profile compared to baseline and PC in prediction of NIV failure.

Dasatinib: a potential tyrosine kinase inhibitor to fight against multiple cancer malignancies.

Dasatinib is the 2nd generation TKI (Tyrosine Kinase Inhibitor) having the potential to treat numerous forms of leukemic and cancer patients and it is 300 times more potent than imatinib. Cancer is the major cause of death globally and need to enumerate novel strategies to coping with it. Various novel therapeutics introduced into the market for ease in treating various forms of cancer. We reviewed and evaluated all the related aspects of dasatinib, which can enhance the knowledge about dasatinib therapeutics methodology, pharmacodynamic and pharmacokinetics, side effects, advantages, disadvantages, various kinds of interactions and its novel formulations as well.

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study.

Background Obesity may alter tissue distribution and clearance of several drugs, especially lipophilic ones. Itraconazole, a lipophilic drug, has been recently introduced in a super-bioavailable formulation (SB-ITZ) for the treatment of dermatophytosis. Evidence regarding optimal dosing of SB-ITZ in obesity is lacking. A current experimental study was planned to analyze tissue concentrations of SB-ITZ at different doses in obese and non-obese rats.  Materials and methods Thirty-six Wistar albino rats of either sex were divided into obese and non-obese rats equally. Further, rats in both categories were divided into three dosing groups. Group 1 received SB-ITZ 13 mg once daily in the morning, group 2 received SB-ITZ 13 mg in the morning and 6.5 mg in the evening, while Group 3 rats received SB-ITZ 13 mg twice daily, orally. Concentrations of SB-ITZ in the skin, serum, and fatty tissue were assessed in each group on days 7, 14, 21, and 28. Comparison of SB-ITZ concentrations in various tissues in obese and non-obese rats and inter-group comparison of tissue concentrations across the three dosing regimens was done at day 28 and expressed as Mean ± SD.36 Wistar rats were divided into obese and non-obese rats equally. Results At day 28, skin concentrations of SB-ITZ were 5.36±1.1, 8.9±1.7 and 10.13±1.7 µg/g in Groups 1, 2, and 3, respectively, in non-obese rats, which was statistically significant (p<0.05) than skin concentration of obese rats (2.72±0.6, 4.2±0.7 and 4.66±0.5 µg/g) for the corresponding dosing groups respectively. Skin concentration of SB-ITZ was statistically significant for Groups 2 and 3 as compared to Group 1. Still, no statistically significant difference was noted between Groups 2 and 3 in non-obese and obese rats. Fatty tissue concentration of SB-ITZ was comparable in all 3 dosing regimens in non-obese and obese rats. But on the intergroup comparison, a statistically significant difference was observed for Groups 2 and 3 against Group 1 (p<0.05). Increasing the dose of SB-ITZ increased serum concentration. In non-obese rats, a statistically significant difference was noted between Group 2 (74.33±6.6 ng/ml) and Group 1 (52.5±9.9 ng/ml); p<0.01 and also in Group 3 (81.33±6.8 ng/ml) against Group 1; p<0.01. Group 3 achieved significantly higher concentration than the other two groups in obese rats (Group 3; 72±5.3, Group 2; 60.5±4.3, and Group 1; 45±7 ng/ml; p<0.01). Conclusion Overall, skin, fatty tissue, and serum concentrations of SB-ITZ were higher in non-obese rats compared to obese rats in all three dosing groups. Moreover, skin and fatty tissue concentrations were proportionately higher than serum in all the groups in non-obese and obese rats. Though the skin concentration of non-obese rats was significantly higher than obese rats, skin concentration in obese rats was within the minimum inhibitory concentration (MIC) range, demonstrating the efficacy of all dosing regimens.