AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

A rolling ball like mass in right atrium of a 6 year old child

Cardiac myxoma is a common tumor occurring more commonly in the left atrium in adult females. Its occurrence in pediatric age group is rare; the more common tumors are rhabdomyoma and fibroma. Presentation of myxoma on the right side is still rarer in this age group. We report a case of a 6-year-old male child who presented with prolonged fever. On examination, there is an extra diastolic sound with mid-diastolic murmur. Echocardiogram is suggestive of a large ball-like polypoidal mass rolling in the right atrium traversing into the right ventricle. The case was immediately operated, and histopathology confirmed the tumor as myxoma. High index of suspicion is required to diagnose the condition to prevent disastrous complications as the presentation is often enigmatic because of vague constitutional findings in most of the cases

A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization

Navya Sree Kola Srinivas,1 Ruchi Verma,2 Girish Pai Kulyadi,1 Lalit Kumar1 1Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit® RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation. To study the effect of CMAs and CPPs, 23 full factorial design was applied. The particle size, polydispersity index, and zeta potential of the optimized solution were 248.20 nm, 0.391, and -5.62 mV, respectively. Drug content of the optimized nanoformulation was found to be 87.74%±1.19%. Atomic force microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are smooth and spherical in nature. In vitro cytotoxicity studies of the nanosuspension on Vero cell line revealed that the formulation is nontoxic. The gefitinib nanosuspension released 60.03%±4.09% drug over a period of 84 h, whereas standard drug dispersion released only 10.39%±3.37% drug in the same duration. From the pharmacokinetic studies, half-life, Cmax, and Tmax of the drug of an optimized nanosuspension were found to be 8.65±1.99 h, 46,211.04±5,805.97 ng/mL, and 6.67±1.77 h, respectively. A 1.812-fold increase in relative bioavailability of nanosuspension was found, which confirmed that the present formulation is suitable to enhance the oral bioavailability of gefitinib. Keywords: gefitinib, cancer, epidermal growth factor receptor tyrosine kinase receptors inhibitor, bioavailability, Eudragit® RL100, PVP K30, PVA, Biopharmaceutical Classification System class II, QbD, design of experiment, full factorial desig

Synthesis and characterization of 9,10-bis(2-phenyl-1,3,4-oxadiazole) derivatives of anthracene: Efficient n-type emitter for organic light-emitting diodes

With a general aim to make anthracene derivatives multifunctional (n-type emitter) and also study their suitability as electron transport layers for organic light emitting diodes (OLED), and with a more specific interest to understand the charge transport and packing pattern in the solid state due to the rotating side rings, we report the synthesis and characterization of six novel molecules (5–10) in which the 9 and 10 positions of anthracene have been directly substituted by phenyloxadiazole groups. We have carried out detailed studies of these molecules including photophysical, electrochemical, electroluminescent studies and solid state structure determination through crystallographic techniques. The electron affinity is very high, around 3.1–3.2 eV, and the ionization potential is around 5.9–6.0 eV, comparable to the more commonly used electron transport electroluminescent layer Alq3. The studies reveal that the new molecules being reported by us, in addition to the high thermal stability, are quite efficient in a two layer unoptimized device with the device structure ITO/α-NPD/5–10/LiF/Al and have an emission in pure green. They also show very high efficiency as electron transport layer in device structure ITO(120nm)/α-NPD(30nm)/Ir(ppy)3 doped CBP(35nm)/BCP(6nm)/5(28nm)/Al(150nm). From these studies we conclude that the anthracene derivatives also have considerable potential as multifunctional layers and as electron transport layers in OLED

Synthesis and characterization of novel 2,5-diphenyl-1,3,4-oxadiazole derivatives of anthracene and its application as electron transporting blue emitters in OLEDs

With a general aim to make anthracene derivatives multifunctional (n-type emitter) and also study their suitability as electron transport layers for organic light emitting diodes (OLED), we report the synthesis and characterization of five novel molecules in which the 9 and 10 positions of anthracene have been directly substituted by 2,5-diphenyl-1,3,4-oxadiazole groups. We have carried out detailed characterization of these molecules which include photophysical, electrochemical, thermal, electroluminescent and computational studies. The electron affinity is very high, around 3.7 eV, and the ionization potential is around 6.7–6.8 eV, which is relatively higher than the most commonly used electron transport electroluminescent layer Alq3. The studies reveal that the new molecules being reported by us, in addition to the high thermal stability, are quite efficient in a two layer unoptimized nondoped device with the device structure ITO/α-NPD/10a–11b/LiF/Al and have an emission in pure blue. They also show very high efficiency as electron transport layer in device structure ITO(120 nm)/α-NPD(30 nm)/Ir(ppy)3 doped CBP(35 nm)/BCP(6 nm)/10a(28 nm)/LiF(1 nm)/Al(150 nm). From these studies we conclude that these anthracene derivatives also have considerable potential as multifunctional layers and as electron transport layers in OLED

Synthesis and Characterization of a Pyromellitic Diimide-Based Polymer with C- and N-Main Chain Links: Matrix for Solution-Processable n-Channel Field-Effect Transistors

A highly soluble pyromellitic diimide-based polymer was obtained through imidization polymerization. The novel architecture features diimide subunits linked alternately at 3,6 and <i>N</i>,<i>N</i>′ positions. The polymer is highly transparent in the near-ultraviolet–visible regions. Smooth and uniform thin-films were obtained through spin-coating even after blending the polymer with PCBM in 1:9 polymer/PCBM weight ratio. While the polymer itself has modest electron mobility in typical bottom-gate top-contact OFETs, an electron mobility of 3 × 10^–3 cm² V^–1 s^–1 was achieved for the blend, which increased to 10^–2 cm² V^–1 s^–1 on exposure to propylamine. Thus, polyimides are demonstrated as promising binder materials for solution-processable n-channel semiconductor blends, of which very few examples are known

A pilot randomized controlled trial to compare the effectiveness of two 14-day primaquine regimens for the radical cure of vivax malaria in South India

Abstract Background Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course. Methods A two centre, randomized, open-label, two arm study was conducted in South India. Patients were randomized to receive either high dose (0.5 mg base/kg body weight) or conventional dose (0.25 mg/kg) PQ for 14 days. Plasma concentrations of PQ and carboxyprimaquine (CPQ) on the 7th day of treatment were measured by reverse phase high performance liquid chromatography. Study subjects were followed up for 6 months. Recurrent infections were genotyped using capillary fragment length polymorphism of two PCR-amplified microsatellite markers (MS07 and MS 10). Results Fifty patients were enrolled. Baseline characteristics and laboratory features did not differ significantly between the groups. Mean age of the study population was 42 ± 16.0 years. Recurrences 80–105 days later occurred in 4 (8%) patients, two in each the groups. All recurrences had the same microsatellite genotype as that causing the index infection suggesting all were relapses. One relapse was associated with low CPQ concentrations suggesting poor adherence. Conclusions This small pilot trial supports the effectiveness of the currently recommended lower dose (0.25 mg/kg/day) 14 day PQ regimen for the radical cure of vivax malaria in South India. Trial registration Clinical Trials Registry-India, CTRI/2017/03/007999. Registered 3 March 2017, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366

Ultrafast Interfacial Charge-Transfer Dynamics in a Donor-π-Acceptor Chromophore Sensitized TiO₂ Nanocomposite

The dynamics of interfacial charge transfer across (<i>E</i>)-3-(5-((4-(9H-carbazol-9-yl)­phenyl)­ethynyl)­thiophen-2-yl)-2-cyanoacrylic acid (CT-CA) and TiO₂ nanocomposites was studied with femtosecond transient absorption, fluorescence upconversion, and molecular quantum dynamics simulations. The investigated dye, CT-CA is a push–pull chromophore that has an intramolecular charge-transfer (ICT) excited state and binds strongly with the surface of TiO₂ nanoparticles. Ultrafast transient absorption and fluorescence measurements, in both solution and thin film samples, were carried out to probe the dynamics of electron injection and charge recombination. Multiexponential electron injection with time constants of <150 fs, 850 fs, and 8.5 ps were observed from femtosecond fluorescence measurements in solution and on thin films. Femtosecond transient absorption measurements show similar multiexponential electron injection and confirm that the picosecond electron injection component arises from the excited ICT state of the CT-CA/TiO₂ complex. Quantum dynamics calculations also show the presence of a slow component (30%) in the electron injection dynamics although most of the electron injection (70%) takes place in less than 20 fs. The slow component of electron injection, from the local ICT state, is attributed to the energetic position of the excited state, which is close to, or slightly below, the conduction band edge. In addition, the transient bleach of CT-CA on the TiO₂ surface is shifted to longer wavelengths when compared to its absorption spectrum and the transient bleach is further shifted to longer wavelengths with charge recombination. These features are attributed to transient Stark shifts that arise from the local electric fields generated at the dye/TiO₂ interface due to charge-transfer interactions