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https://www.readbyqxmd.com/read/29449715/leptin-and-brain-adipose-crosstalks
#1
REVIEW
Alexandre Caron, Syann Lee, Joel K Elmquist, Laurent Gautron
Interactions between the brain and distinct adipose depots have a key role in maintaining energy balance, thereby promoting survival in response to metabolic challenges such as cold exposure and starvation. Recently, there has been renewed interest in the specific central neuronal circuits that regulate adipose depots. Here, we review anatomical, genetic and pharmacological studies on the neural regulation of adipose function, including lipolysis, non-shivering thermogenesis, browning and leptin secretion. In particular, we emphasize the role of leptin-sensitive neurons and the sympathetic nervous system in modulating the activity of brown, white and beige adipose tissues...
February 16, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29447836/sensory-denervation-of-inguinal-white-fat-modifies-sympathetic-outflow-to-white-and-brown-fat-in-siberian-hamsters
#2
REVIEW
Ngoc Ly T Nguyen, Bingzhong Xue, Timothy J Bartness
White adipose tissue (WAT) and brown adipose tissue (BAT) have sympathetic nervous system (SNS) and sensory innervations. Previous studies from our laboratory revealed central neuroanatomical evidence of WAT sensory and BAT SNS crosstalk with double labeling of inguinal WAT (IWAT) sensory and interscapular BAT (IBAT) SNS neurons. We previously demonstrated that WAT lipolysis increases IBAT temperature, but this effect is absent when IWAT afferents are surgically denervated, which severs both sensory and SNS nerves...
February 12, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29446744/delivery-of-peptidic-gonadotropin-releasing-hormone-antagonists
#3
Rawda Yaseen AlSheyyab, Bashar Mohammad Al-Taani, Rana Mohammad Obeidat, Motasem Mohammad Alsmadi, Rafeef Khalid Masaedeh, Raghda Nasry Sabat
GnRH antagonists have several clinical applications in prostate cancer, regulation of ovulation induction in females, breast cancer, male contraception and others. Antagonists differ from natural GnRH decapeptide in having five or more amino acid substitutions. Whereas most of antagonists are available as subcutaneous (SC) formula for injection, some are formulated as a depot formulation for sustained release (e.g. Cetrarelix, Degarelix). Systemic delivery of cetrorelix acetate by intratracheal route can be achieved using dry powder for inhalation of adhesive mixture when the powder deposition reaches stage four...
February 14, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29440894/sustained-release-of-fgf-2-from-a-hybrid-hydrogel-of-heparin-poloxamer-and-decellular-matrix-promotes-the-neuroprotective-effects-of-proteins-after-spinal-injury
#4
He-Lin Xu, Fu-Rong Tian, Jian Xiao, Pian-Pian Chen, Jie Xu, Zi-Liang Fan, Jing-Jing Yang, Cui-Tao Lu, Ying-Zheng Zhao
Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI). Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP), as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM) as an affinity depot of drug...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29437029/formulation-and-in-vitro-and-ex-vivo-evaluation-of-tretinoin-loaded-cubosomal-gel-for-acne-treatment
#5
Gaurav Gupta, Shruti Sureka
OBJECTIVE: The current work was attempted to formulate and evaluate the topical sustained release delivery systems potential of bicontinuous cubic monoglyceride -water phases - 'cubosomes' containing Tretinoin with an opinion to sustain the release of drug in the acne treatment. METHODS: Tretinoin loaded cubosomes were prepared by bottom-up technique, by varying the concentration of lipid and surfactant and keeping the drug concentration constant, made a total of nine formulations of tretinoin as TCF...
February 13, 2018: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29436835/pharmacokinetic-and-chemical-synthesis-optimization-of-a-potent-d-peptide-hiv-entry-inhibitor-suitable-for-extended-release-delivery
#6
Joseph S Redman, J Nicholas Francis, Robert Marquardt, Damon Papac, Alan L Mueller, Debra M Eckert, Brett D Welch, Michael S Kay
Peptides often suffer from short in vivo half-lives due to proteolysis and renal clearance that limit their therapeutic potential in many indications, necessitating pharmacokinetic (PK) enhancement. D-peptides, composed of mirror-image D-amino acids, overcome proteolytic degradation but are still vulnerable to renal filtration due to their small size. If renal filtration could be slowed, D-peptides would be promising therapeutic agents for infrequent dosing, such as in extended-release depots. Here, we tether a diverse set of PK-enhancing cargoes to our potent, protease-resistant D-peptide HIV entry inhibitor, PIE12-trimer...
February 13, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29436172/population-pharmacokinetic-pharmacodynamic-pk-pd-modeling-of-depot-testosterone-cypionate-in-healthy-male-subjects
#7
Youwei Bi, Paul J Perry, Michael Ellerby, Daryl J Murry
A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate. Thirty-one healthy males were randomized into a dose group of 100, 250 or 500mg/wk and received 14 weekly injections of TC. A PK-PD model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone...
February 13, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29430842/glucagon-like-peptide-1-glp-1-based-therapeutics-current-status-and-future-opportunities-beyond-type-2-diabetes
#8
Jia Ying Cheang, Peter Michael Moyle
Glucagon-like peptide-1 (GLP-1) is secreted by intestinal L-cells following food intake, and plays an important role in glucose homeostasis due to its stimulation of glucose-dependent insulin secretion. Further, GLP-1 is also associated with protective effects on pancreatic β-cells and the cardiovascular system, reduced appetite, and weight loss, making GLP-1 derivatives an exciting treatment for type 2 diabetes and obesity. Despite these benefits, wild-type GLP-1 exhibits a short circulation time, due to its poor metabolic stability and rapid renal clearance, and needs to be administered by injection, making it a poor therapeutic agent...
February 11, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29427237/differential-expression-of-lp-pla2-in-obesity-and-type-2-diabetes-and-the-influence-of-lipids
#9
Laura Jackisch, Warunee Kumsaiyai, Jonathan D Moore, Nasser Al-Daghri, Ioannis Kyrou, Thomas M Barber, Harpal Randeva, Sudhesh Kumar, Gyanendra Tripathi, Philip G McTernan
AIMS/HYPOTHESIS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2...
February 9, 2018: Diabetologia
https://www.readbyqxmd.com/read/29425770/scarring-vs-functional-healing-matrix-based-strategies-to-regulate-tissue-repair
#10
Timothy J Keane, Christine-Maria Horejs, Molly M Stevens
All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosis is a process that stands diametrically opposed to functional tissue regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. Wound healing is guided by precise spatiotemporal deposition and remodelling of the extracellular matrix (ECM)...
February 6, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29425108/neck-adipose-tissue-tying-ties-in-metabolic-disorders
#11
REVIEW
Vlatka Pandzic Jaksic, Danijela Grizelj, Ana Livun, Drago Boscic, Marko Ajduk, Rajko Kusec, Ozren Jaksic
Upper body adipose tissue accumulation has been associated with clustering of metabolic disorders and increased cardiovascular risk. Neck circumference (NC) indicated that subcutaneous adipose tissue (SAT) in that region is an independent pathogenic depot that might account for the additional risk missed by visceral adipose tissue (VAT). Neck adipose tissue (NAT) is not only one more ectopic depot but has several particular features that might modulate its metabolic role. Besides a controversial impact on obstructive apnea syndrome, neck fat encompasses carotid arteries as an important perivascular adipose tissue (PVAT) depot...
February 9, 2018: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/29424291/hydrogel-formulations-for-biologicals-current-spotlight-from-a-commercial-perspective
#12
Ludger M Ickenstein, Patrick Garidel
Hydrogels are, from a commercial perspective especially because of their ease of production, attractive sustained-release systems for high potent immunoglobulins with short circulation half-lives. Hydrogel formulations can reduce the dosing frequency while maintaining therapeutically relevant drug concentrations locally as well as systemically. However, hydrogels have only limited loading capacities and release hydrophilic immunoglobulins typically within hours or days, whereas weeks or months would be more preferable...
February 1, 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/29423731/hiv-persistence-in-adipose-tissue-reservoirs
#13
REVIEW
Jacob Couturier, Dorothy E Lewis
PURPOSE OF REVIEW: The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. RECENT FINDINGS: Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue...
February 9, 2018: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/29413493/supplementation-of-suckling-rats-with-cow-s-milk-induces-hyperphagia-and-higher-visceral-adiposity-in-females-at-adulthood-but-not-in-males
#14
Vanessa Silva Tavares Rodrigues, Egberto Gaspar Moura, Dayse Nascimento Bernardino, Janaine Cavalcanti Carvalho, Patricia Novaes Soares, Thamara Cherem Peixoto, Nayara Peixoto-Silva, Elaine Oliveira, Patricia Cristina Lisboa
In humans, complementary feeding should be started after 6 months-old; the introduction of any food or water before this time is considered early weaning, which is associated with health problems in adulthood. Cow's milk is a common food introduced to children less than 6 months that has inadequate nutritional composition mainly due to a worse casein: whey protein ratio compared to human milk. We hypothesized that suckling rats fed with cow's milk, rich in bioactive peptides, develop further metabolic dysfunctions...
December 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29412837/glucose-lowering-therapies-in-type-2-diabetes-opportunities-and-challenges-for-peptides
#15
REVIEW
Clifford J Bailey
This overview considers the opportunities and challenges that face the use of gluco-regulatory peptides to treat type 2 diabetes. New insulin analogues and formulations are being developed with pharmacokinetic properties to speed-up or prolong transfer from a subcutaneous injection site to the target tissues, or to selectively favour effects on the liver. Alternative routes of insulin administration continue to attract attention, and advances in the integration of glucose monitoring with insulin pump devices are improving miniaturised 'closed loop' artificial pancreas systems...
February 2018: Peptides
https://www.readbyqxmd.com/read/29410017/differential-response-to-caloric-restriction-of-retroperitoneal-epididymal-and-subcutaneous-adipose-tissue-depots-in-rats
#16
Takumi Narita, Masaki Kobayashi, Kaho Itakura, Rei Itagawa, Riho Kabaya, Yuka Sudo, Naoyuki Okita, Yoshikazu Higami
The beneficial actions of caloric restriction (CR) are partially mediated by metabolic remodeling of white adipose tissue (WAT). Recently, we showed that CR enhances de novo fatty acid (FA) biosynthesis and mitochondrial biogenesis, particularly in WAT. Here, to better understand the response of WAT to CR, we compare the effects of CR on three WAT depots in rats: retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous (sWAT). Computed tomography and histological analysis showed that CR reduced the volume and average size of rWAT adipocytes...
February 1, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29409985/transforming-growth-factor-beta-superfamily-regulation-of-adipose-tissue-biology-in-obesity
#17
REVIEW
Mi-Jeong Lee
Accumulation of dysfunctional white adipose tissues increases risks for cardiometabolic diseases in obesity. In addition to white, brown or brite adipose tissues are also present in adult humans and increasing their amount may be protective. Therefore, understanding factors regulating the amount and function of each adipose depot is crucial for developing therapeutic targets for obesity and its associated metabolic diseases. The transforming growth factor beta (TGFβ) superfamily, which consists of TGFβ, BMPs, GDFs, and activins, controls multiple aspects of adipose biology...
January 30, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29409758/postprandial-regulation-of-natriuretic-peptides-in-vivo-and-of-their-receptors-by-fatty-acids-in-adipocytes-in-vitro
#18
Andreas Schmid, Jens Albrecht, Judith Brock, Maria Koukou, Efthymia Arapogianni, Andreas Schäffler, Thomas Karrasch
BACKGROUND AND AIM: Natriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B, NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44). PATIENTS, MATERIAL AND METHODS: The postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100)...
January 30, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29408551/dual-dye-in-vivo-imaging-of-differentially-charged-plga-carriers-reveals-antigen-depot-effect-leading-to-improved-immune-responses-in-preclinical-models
#19
Markus Riehl, Meike Harms, Henrike Lucas, Thomas Ebensen, Carlos A Guzmán, Karsten Mäder
The present in-vivo study investigated the behavior and performance of differently charged poly(lactic‑co‑glycolic) acid microparticles (PLGA MP) as vaccination platform. For this purpose, particles loaded with Ovalbumin (OVA) as model antigen were subcutaneously (s.c.) injected in SKH1 mice. The utilized SKH1 hairless mice exhibit a fully operative immune system and allow parallel imaging investigations due to the lack of hair. Usage of this species enabled the combination of two investigations within a single study protocol, namely noninvasive in-vivo imaging and immune responses directed towards the antigen...
February 2, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29408184/-us-detonated-nano-bombs-facilitate-targeting-treatment-of-resistant-breast-cancer
#20
Jinjin Shi, Wei Liu, Yu Fu, Na Yin, Hongling Zhang, Junbiao Chang, Zhenzhong Zhang
Reversal of drug resistance and targeted therapy are the keys but remain challenging in resistant breast cancer treatment. Herein, low frequency ultrasound detonated "nano bombs" were rationally designed and used for treatment of resistant breast cancer. For the 'nano bombs', the ammunition (Doxorubicin, DOX) was loaded into the ammunition depot (hollow mesoporous TiO2, MTNs), and the safety device (dsDNA) was wrapped on the surface of MTNs to avoid the unexpected DOX release. We found the "US-detonated explosive" abilities of "nano bomb" MTNs (NBMTNs), including explosive generation of ROS, explosive release of DOX, US-triggered lysosome escape and mitochondrial targeting in the in vitro and in vivo studies...
February 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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