Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.

Background and aims: Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function. Methods and results: Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding. Conclusion: IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.

Physiological and biochemical effects of 24-Epibrassinolide on drought stress adaptation in maize (Zea mays L.).

Maize production and productivity are affected by drought stress in tropical and subtropical ecologies, as the majority of the area under maize cultivation in these ecologies is rain-fed. The present investigation was conducted to study the physiological and biochemical effects of 24-Epibrassinolide (EBR) as a plant hormone on drought tolerance in maize. Two maize hybrids, Vivek hybrid 9 and Bio 9637, were grown under three different conditions: (i) irrigated, (ii) drought, and (iii) drought+EBR. A total of 2 weeks before the anthesis, irrigation was discontinued to produce a drought-like condition. In the drought+EBR treatment group, irrigation was also stopped, and in addition, EBR was applied as a foliar spray on the same day in the drought plots. It was observed that drought had a major influence on the photosynthesis rate, membrane stability index, leaf area index, relative water content, and leaf water potential; this effect was more pronounced in Bio 9637. Conversely, the activities of antioxidant enzymes such as catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) increased in both hybrids under drought conditions. Specifically, Vivek hybrid 9 showed 74% higher CAT activity under drought conditions as compared to the control. Additionally, EBR application further enhanced the activity of this enzyme by 23% compared to plants under drought conditions. Both hybrids experienced a significant reduction in plant girth due to drought stress. However, it was found that exogenously applying EBR reduced the detrimental effects of drought stress on the plant, and this effect was more pronounced in Bio 9637. In fact, Bio 9637 treated with EBR showed an 86% increase in proline content and a 70% increase in glycine betaine content compared to untreated plants under drought conditions. Taken together, our results suggested EBR enhanced tolerance to drought in maize hybrids. Hence, pre-anthesis foliar application of EBR might partly overcome the adverse effects of flowering stage drought in maize.

Case report: Antidromic atrioventricular reentrant tachycardia and underlying Ebstein anomaly.

Multiple accessory pathways (APs) can develop in patients with Ebstein anomaly. Rarely, these APs can participate in antidromic atrioventricular reentrant tachycardia (AVRT) which can be life-threatening and requires unique considerations for acute management and ultimate ablation. These considerations are discussed herein.

Hyaluronic acid-oleylamine and chitosan-oleic acid conjugate-based hybrid nanoparticle delivery via. dissolving microneedles for enhanced treatment efficacy in localized breast cancer.

Microneedle technology offers a minimally invasive treatment strategy to deliver chemotherapeutics to localized tumors. Amalgamating the surface functionalized nanoparticles with microneedle technology can potentially deliver drugs directly to tumors and subsequently target cancer cells via, overexpressed receptors on the cell surface, thereby enhancing the treatment efficacy while reducing side effects. Here, we report cetuximab anchored hyaluronic acid-oleylamine and chitosan-oleic acid-based hybrid nanoparticle (HA-OA/CS-OA NPT)-loaded dissolving microneedles (MN) for targeted delivery of cabazitaxel (CBT) in localized breast cancer tumor. The HA-OA/CS-OA NPT was characterized for their size, surface charge, morphology, physicochemical characteristics, drug release behavior, and in vitro anti-cancer efficacy. The HA-OA/CS-OA NPT were of ~125 nm size, showed enhanced cytotoxicity and cellular uptake, and elicited a superior apoptotic response against MDA-MB-231 cells. Subsequently, the morphology and physicochemical characteristics of HA-OA/CS-OA NPT-loaded MN were also evaluated. The fabricated microneedles were of ~550 µm height and showed loading of nanoparticles equivalent to ~250 µg of CBT. The ex vivo skin permeation study revealed fast dissolution of microneedles upon hydration, while the drug permeation across the skin exhibited ~4-fold improvement in comparison to free drug-loaded MN. In vivo studies performed on DMBA-induced breast cancer in female SD rats showed a marked reduction in tumor volume after administration of drug and nanoparticle-loaded microneedles in comparison to intravenous administration of free drug. However, the HA-OA/CS-OA NPT-MN showed the highest tumor reduction and survival rate, with the lowest body weight reduction in comparison to other treatment groups, indicating its superior efficacy and low systemic toxicity. Overall, the dissolving microneedle-mediated delivery of targeted nanoparticles loaded with chemotherapeutics offers a superior alternative to conventional intravenous chemotherapy.

Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.

Approach to the patient: Concept and application of targeted radiotherapy in the paraganglioma patient.

Paragangliomas can metastasize, posing potential challenges in both symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another one. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. As conclusion, perspectives in radiotherapies of paraganglioma patients are outlined since they hold near future promising approaches that can improve patient outcomes.

Weakly Supervised Detection of Pheochromocytomas and Paragangliomas in CT.

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors which have the potential to metastasize. For the management of patients with PPGLs, CT is the preferred modality of choice for precise localization and estimation of their progression. However, due to the myriad variations in size, morphology, and appearance of the tumors in different anatomical regions, radiologists are posed with the challenge of accurate detection of PPGLs. Since clinicians also need to routinely measure their size and track their changes over time across patient visits, manual demarcation of PPGLs is quite a time-consuming and cumbersome process. To ameliorate the manual effort spent for this task, we propose an automated method to detect PPGLs in CT studies via a proxy segmentation task. As only weak annotations for PPGLs in the form of prospectively marked 2D bounding boxes on an axial slice were available, we extended these 2D boxes into weak 3D annotations and trained a 3D full-resolution nnUNet model to directly segment PPGLs. We evaluated our approach on a dataset consisting of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. We obtained a precision of 70% and sensitivity of 64.1% with our proposed approach when tested on 53 CT studies. Our findings highlight the promising nature of detecting PPGLs via segmentation, and furthers the state-of-the-art in this exciting yet challenging area of rare cancer management.

Lipid-coated nanocrystals of paclitaxel as dry powder for inhalation: Characterization, in-vitro performance, and pharmacokinetic assessment.

BACKGROUND: Nanocrystals can be produced as a dry powder for inhalation (DPIs) to deliver high doses of drug to the lungs, owing to their high payload and stability to the shear stress of aerosolization force. Furthermore, lipid-coated nanocrystals can be formulated to improve the drug accumulation and retention in lung. OBJECTIVE: The present work involved the fabrication of paclitaxel nanocrystals using hydrophilic marine biopolymer fucoidan as a stabilizer. Thereafter, fabricated nanocrystals (FPNC) were surface-modified with phospholipid to give lipid-coated nanocrystals (Lipo-NCs). METHODS: The nanocrystals were fabricated by antisolvent crystallization followed by the probe sonication. The lipid coating was achieved by thin film hydration followed ultrasonic dispersion technique. Prepared nanocrystals were lyophilized to obtain a dry powder of FPNC and Lipo-NCs, used later for physicochemical, microscopic, and spectroscopic characterization to confirm the successful formation of desired nanocrystals. In-vitro and in-vivo investigations were also conducted to determine the role of nanocrystal powder in pulmonary drug delivery. RESULTS: Lipo-NCs exhibited slower drug release, excellent flow properties, good aerosolization performance, higher drug distribution, and prolonged retention in the lungs compared to FPNC and pure PTX. CONCLUSION: Lipid-coated nanocrystals can be a novel formulation for the maximum localization of drugs in the lungs, thereby enhancing therapeutic effects and avoiding systemic side effects in lung cancer therapy.

Biopolymer-based tumor microenvironment-responsive nanomedicine for targeted cancer therapy.

Nanomedicine has opened up new avenues for cancer treatment by enhancing drug solubility, permeability and targeted delivery to cancer cells. Despite its numerous advantages over conventional therapies, nanomedicine may exhibit off-target drug distribution, harming nontarget regions. The increased permeation and retention effect of nanomedicine in tumor sites also has its limitations, as abnormal tumor vasculature, dense stroma structure and altered tumor microenvironment (TME) may result in limited intratumor distribution and therapeutic failure. However, TME-responsive nanomedicine has exhibited immense potential for efficient, safe and precise delivery of therapeutics utilizing stimuli specific to the TME. This review discusses the mechanistic aspects of various TME-responsive biopolymers and their application in developing various types of TME-responsive nanomedicine.

Fabrication of gelatin coated polycaprolactone nanofiber scaffolds co-loaded with luliconazole and naringenin for treatment of Candida infected diabetic wounds.

The current study focuses on the development of gelatin-coated polycaprolactone (PCL) nanofibers co-loaded with luliconazole and naringenin for accelerated healing of infected diabetic wounds. Inherently, PCL nanofibers have excellent biocompatibility and biodegradation profiles but lack bioadhesion characteristics, which limits their use as dressing materials. So, coating them with a biocompatible and hydrophilic material like gelatin can improve bioadhesion. The preparation of nanofibers was done with the electrospinning technique. The solid state characterization and in-vitro performance assessment of nanofibers indicate the formation of uniformly interconnected nanofibers of 200-400 nm in diameter with smooth surface topography, excellent drug entrapment, and a surface pH of 5.6-6.8. The antifungal study showed that the nanofiber matrix exhibits excellent biofilm inhibition activity against several strains of Candida. Further, in-vivo assessment of nanofiber performance on C. albicans infected wounds in diabetic rats indicated accelerated wound healing efficacy in comparison to gauge-treated groups. Additionally, a higher blood flow and rapid re-epithelialization of wound tissue in the treatment group corroborated with the results obtained in the wound closure study. Overall, the developed dual-drug-loaded electrospun nanofiber mats have good compatibility, surface properties, and excellent wound healing potential, which can provide an extra edge in the management of complex diabetic wounds.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

Formulation and characterization of polyvinyl alcohol/chitosan composite nanofiber co-loaded with silver nanoparticle & luliconazole encapsulated poly lactic-co-glycolic acid nanoparticle for treatment of diabetic foot ulcer.

Chronic wounds are prone to fungal infections, possess a significant challenge, and result in substantial mortality. Diabetic wounds infected with Candida strains are extremely common. It can create biofilm at the wound site, which can lead to antibiotic resistance. As a result, developing innovative dressing materials that combat fungal infections while also providing wound healing is a viable strategy to treat infected wounds and address the issue of antibiotic resistance. Present work proposed anti-infective dressing material for the treatment of fungal strains Candida-infected diabetic foot ulcer (DFU). The nanofiber was fabricated using polyvinyl Alcohol/chitosan as hydrogel base and co-loaded with silver nanoparticles (AgNP) and luliconazole-nanoparticles (LZNP) nanoparticles, prepared using PLGA. Fabricated nanofibers had pH close to target area and exhibited hydrophilic surface suitable for adhesion to wound area. The nanofibers showed strong antifungal and antibiofilm properties against different strains of Candida; mainly C. albicans, C. auris, C. krusei, C. parapsilosis and C. tropicalis. Nanofibers exhibited excellent water retention potential and water vapour transmission rate. The nanofibers had sufficient payload capacity towards AgNP and LZNP, and provided controlled release of payload, which was also confirmed by in-vivo imaging. In-vitro studies confirmed the biocompatibility and enhanced proliferation of Human keratinocytes cells (HaCaT). In-vivo studies showed accelerated wound closure by providing ant-infective action, supporting cellular proliferation and improving blood flow, all collectively contributing in expedited wound healing.

Fabrication of dual drug-loaded polycaprolactone-gelatin composite nanofibers for full thickness diabetic wound healing.

Aim: Design of moxifloxacin and ornidazole co-loaded polycaprolactone and gelatin nanofiber dressing for diabetic wounds. Materials & methods: The composite nanofibers were prepared using electrospinning technique and characterized for in vitro drug release, antibacterial activity, laser doppler and in vivo wound healing. Results: The optimized nanofiber demonstrated an interconnected bead free nanofiber with average diameter <200 nm. The in vitro drug release & antimicrobial studies revealed that optimized nanofiber provided drug release for >120 h, thereby inhibiting growth of Escherichia coli and Stapyhlococcus aureus. An in vivo wound closure study on diabetic rats found that optimized nanofiber group had a significantly higher wound closure rate than marketed formulation. Conclusion: The nanofiber provided prolonged drug release and accelerated wound healing, making it a promising candidate for diabetic wound care.

This article is about making a wound dressing material of tiny fibres that have antibiotic properties to kill microbes at the wound site and make wounds heal faster. This is particularly important for people with diabetes, whose wounds often take longer to heal. The designed nanofibrous dressing releases antibiotic drugs at the wound site for more than 120 h, killing harmful microbes and thus avoiding their invasion at wound site. Also, animal experiments showed that the nanofibers shorten the time wounds take to heal by providing a suitable surface and a favourable environment for wound healing. The study concludes that the fabricated nanofiber dressing helps complex wounds heal faster, and could be a strong new dressing material for diabetic wound care.

Development and Evaluation of Amorphous Solid Dispersion of Riluzole with PBPK Model to Simulate the Pharmacokinetic Profile.

In the current work, screening of polymers viz. polyacrylic acid (PAA), polyvinyl pyrrolidone vinyl acetate (PVP VA), and hydroxypropyl methyl cellulose acetate succinate (HPMC AS) based on drug-polymer interaction and wetting property was done for the production of a stable amorphous solid dispersion (ASD) of a poorly water-soluble drug Riluzole (RLZ). PAA showed maximum interaction and wetting property hence, was selected for further studies. Solid state characterization studies confirmed the formation of ASD with PAA. Saturation solubility, dissolution profile, and in vivo pharmacokinetic data of the ASD formulation were generated in rats against its marketed tablet Rilutor. The RLZ:PAA ASD showed exponential enhancement in the dissolution of RLZ. Predicted and observed pharmacokinetic data in rats showed enhanced area under curve (AUC) and Cmax in plasma and brain with respect to Rilutor. Furthermore, a physiologically based pharmacokinetic (PBPK) model of rats for Rilutor and RLZ ASD was developed and then extrapolated to humans where physiological parameters were changed along with a biochemical parameter. The partition coefficient was kept similar in both species. The model was used to predict different exposure scenarios, and the simulated data was compared with observed data points. The PBPK model simulated Cmax and AUC was within two times the experimental data for plasma and brain. The Cmax and AUC in the brain increased with ASD compared to Rilutor for humans showing its potential in improving its biopharmaceutical performance and hence enhanced therapeutic efficacy. The model can predict the RLZ concentration in multiple compartments including plasma and liver.

Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy.

Purpose: While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated. Methods: The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed. Results: Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours. Conclusions: [177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.

Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation.

Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.

Paediatric phaeochromocytoma and paraganglioma: A clinical update.

Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management.

Myricetin encapsulated chitosan nanoformulation for management of type 2 diabetes: Preparation, optimization, characterization and in vivo activity.

Type 2 diabetes mellitus (T2DM) is a serious and alarming disease attracting widespread attention. It is not a single metabolic disease; over time, it leads to serious disorders, namely, diabetic nephropathy, neuropathy, retinopathy and several cardiovascular, hepatocellular complications. The increase in T2DM cases in recent times has attracted significant attention. Currently, the medications available have side effects, and injectables are painful, causing trauma to the patients. Therefore, it is imperative to come up with oral delivery. In this background we report here a nanoformulation carrying natural small molecule Myricetin (MYR) encapsulated within Chitosan nanoparticles (CHT-NPs). MYR-CHT-NPs were prepared by ionic gelation method and evaluated using different characterization techniques. The in vitro release of MYR from CHT NPs in different physiological media showed pH dependence. in vivo pharmacodynamic study followed by oral administration in Albino Wistar rats showed better glycaemic control than existing drug. Further, the optimized nanoparticles also exhibited controlled increase in weight as compared to Metformin. The biochemistry profile of rats treated with nanoformulation reduced the levels of several pathological biomarkers, indicating additional benefits of MYR. Histopathological images exhibited no toxicity or changes in the major organs section in contrast to normal control, suggesting safe oral administration of the encapsulated MYR. Thus, we conclude that MYR-CHT-NPs represent an attractive delivery vehicle in improving the blood glucose level with controlled weight and have the potential to be safely administered orally for the management of T2DM.