bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurogenic tumour of the posterior mediastinum: double the complications
Authors: Abdalla Hani , Bille Andrea , Ong Cheng 
Published: May 2018

SummaryNeurogenic tumours are the most common posterior mediastinal masses. They are usually benign, slow‐growing and can be large enough to cause compression symptoms on surrounding structures, including the airway, heart, great vessels, nerves and ganglia. Anaesthetic management of these patients requires anatomical knowledge of adjacent structures, and an expectant approach to potential complications such as haemorrhage.We present a case of a large, non‐functional neurogenic tumour of the posterior mediastinum with cervical extension that presented with symptoms of sympathetic ganglia blockade. This was resected by cervical and thoracic approaches. Our case highlights intra‐operative management, and the early detection of a subclavian artery stenosis by vigilant monitoring. We also describe our choice for postoperative analgesia and the potential side‐effects mimicking complications of sympathetic trunk resection.
Natural Alkaloids Intervening the Insulin Pathway: New Hopes for Anti-Diabetic Agents?
Authors: Christodoulou Maria-Ioanna , Tchoumtchoua Job , Skaltsounis Alexios-Leandros , Scorilas Andreas , Halabalaki Maria 
Published: May 2018

Background:
Accumulating experimental data supports the capacity of natural
compounds to intervene in complicated molecular pathways underlying the pathogenesis of
certain human morbidities. Among them, diabetes is now a world’s epidemic associated with
increased risk of death; thus, the detection of novel anti-diabetic agents and/or adjuvants is of
vital importance. Alkaloids represent a diverse group of natural products with a range of
therapeutic properties; during the last 20 years, published research on their anti-diabetic capacity
has been tremendously increased.

Purpose:
To discuss current concepts on the anti-diabetic impact of certain alkaloids, with
special reference to their molecular targets throughout the insulin-signaling pathway.

Methodology:
Upon in-depth search in the SCOPUS and PUBMED databases, the literature
on alkaloids with insulin secretion/sensitization properties was critically reviewed.

Results:
In-vitro and in-vivo evidence supports the effect of berberine, trigonelline, piperine,
oxymatrine, vindoneline, evodiamine and neferine on insulin-signaling and related cascades
in beta-cells, myocytes, adipocytes, hepatocytes and other cells. Associated receptors, kinases,
hormones and cytokines, are affected in terms of gene transcription, protein expression, activity
and/or phosphorylation. Pathophysiological processes associated with insulin resistance,
beta-cell failure, oxidative stress and inflammation, as well as clinical phenotype are also influenced.

Discussion:
Growing evidence suggests the ability of specific alkaloids to intervene in the
insulin-signal transduction pathway, reverse molecular defects resulting in insulin resistance
and glucose intolerance and improve disease complications, in-vitro and in-vivo. Future indepth
molecular studies are expected to elucidate their exact mechanism of action, while large
clinical trials are urgently needed to assess their potential as anti-diabetic agents.
Blocking IL-6/GP130 Signaling Inhibits Cell Viability/Proliferation, Glycolysis, and Colony Forming Activity in Human Pancreatic Cancer Cells
Authors: Chen Xiang , Tian Jilai , Su Gloria H. , Lin Jiayuh 
Published: May 2018

Background:Elevated production of the pro-inflammatory cytokine interleukin-6 (IL-6) and dysfunction of IL-6 signaling promotes tumorigenesis and are associated with poor survival outcomes in multiple cancer types. Recent studies showed that the IL-6/GP130/STAT3 signaling pathway plays a pivotal role in pancreatic cancer development and maintenance.Objective:We aim to develop effective treatments through inhibition of IL-6/GP130 signaling in pancreatic cancer.Methods:The effects on cell viability and cell proliferation were measured by MTT and BrdU assays, respectively. The effects on glycolysis was determined by cell-based assays to measure lactate levels. Protein expression changes were evaluated by western blotting and immunoprecipitation. siRNA transfection was used to knock down estrogen receptor α gene expression. Colony forming ability was determined by colony forming cell assay.Results:We demonstrated that IL-6 can induce pancreatic cancer cell viability/proliferation and glycolysis. We also showed that a repurposing FDA-approved drug bazedoxifene could inhibit the IL-6/IL-6R/GP130 complexes. Bazedoxifene also inhibited JAK1 binding to IL-6/IL-6R/GP130 complexes and STAT3 phosphorylation. In addition, bazedoxifene impeded IL-6 mediated cell viability/ proliferation and glycolysis in pancreatic cancer cells. Consistently, other IL-6/GP130 inhibitors SC144 and evista showed similar inhibition of IL-6 stimulated cell viability, cell proliferation and glycolysis. Furthermore, all three IL-6/GP130 inhibitors reduced the colony forming ability in pancreatic cancer cells.Conclusion:Our findings demonstrated that IL-6 stimulates pancreatic cancer cell proliferation, survival and glycolysis, and supported persistent IL-6 signaling is a viable therapeutic target for pancreatic cancer using IL-6/GP130 inhibitors.
Cutaneous Application of Celecoxib for Inflammatory and Cancer Diseases
Authors: Quiñones Oliesia Gonzalez , Pierre Maria Bernadete Riemma 
Published: May 2018

Background:
Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective
cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Cxb) are considered promising cancer chemopreventive
for colon, breast, prostate, lung, and skin cancers. However, the clinical application to
the prevention is limited by concerns about safety, potential to serious toxicity (mainly for healthy individuals),
efficacy and optimal treatment regimen. Cxb exhibits advantages as potent antiinflammatory
and gastrointestinal tolerance compared with conventional NSAID’s. Recent researches
suggest that dermatological formulations of Cxb are more suitable than oral administration in the
treatment of cutaneous disease, including skin cancer. To date, optimism has been growing regarding
the exploration of the topical application of Cxb (in the prevention of skin cancers and treatment of
cutaneous inflammation) or transdermal route reducing risks of systemic side effects.

Objective:
This paper briefly summarizes our current knowledge of the development of the cutaneous
formulations or delivery systems for Cxb as anti-inflammatory drug (for topical or transdermal application)
as well its chemopreventive properties focused on skin cancer.

New perspectives emerge from the growing knowledge, bringing innovative techniques
combining the action of Cxb with other substances or agents which act in a different way, but complementary,
increasing the efficacy and minimizing toxicity.
Multivariate UV-Chemometric and HPLC-QbD Method for Simultaneous Estimation of Vardenafil and Dapoxetine in Active Pharmaceutical Ingredients and its Marketed Formulation
Authors: Patel Mital N. , Kothari Charmy S. 
Published: May 2018

Background:
This manuscript focuses on Novel multivariate UV-chemometric method and
HPLC-QbD method for simultaneous determination of Vardenafil (VR) and Dapoxetine (DP) in active
pharmaceutical ingredient and their marketed formulation. To the best of our knowledge, there is no
literature data on multivariate methods for the same.

Methods:
The spectrophotometric data were processed by CLS, PCR, PLS and MLR methods in order
to determine the active substances, without prior separation from tablet marketed formulation. Analytical
figures of merit, such as sensitivity, selectivity, analytical sensitivity, LOD, and LOQ were determined.
In HPLC-QbD, four critical factors were selected after screening and boxbehnken design was
applied for optimization. Twenty-five experiments were done, and a quadratic model was used for all
response variables. Desirability plot, surface plot, design space, and three-dimensional plots were calculated.

Results:
For Chemometrics, wavelength range selected was 202 nm - 326 nm at 2 nm intervals, hence
59 wavelength points were selected in such a way that minimum RMSEC and RMSECV values were
obtained at multiple wavelengths. HPLC-QbD optimized conditions were; Phenomenex C8 column
(250 × 4.6 mm, 5 μm), acetonitrile: buffer (ammonium acetate buffer at pH 2.7 with acetic acid) (40:60,
v/v) as a mobile phase at flow rate of 0.9 mL/min, 239 nm wavelength and 20°C temperature.

Conclusion:
The developed methods were validated and successfully applied for simultaneous determination
of VR and DP in tablet dosage form. The results obtained by UV-Chemometric methods were
statistically compared with an HPLC-QbD method, which concludes both the methods can apply for
tablet analysis.
RP-HPLC-UV Detection Method for the Simultaneous Determinat ion of Econazole Nitrate, Triamcinolone Acetonide and Benzoic Acid in Ternary Mixture
Authors: EL-Zaher Asmaa A. , Elkady Ehab F. , Al-Tahami Amaal A. 
Published: May 2018

Background:Econazole nitrate and triamcinolone acetonide are one of the topical antifungal corticosteroid fixed combinations. Although this combination has been literately investigated, yet their ternary mixture with benzoic acid as preservative lack of a simple method for its determination.Objective:The objective of this work is to present simple, accurate, precise and low cost reversed-phase liquid chromatography (RP-LC) method for the separation and determination of econazole nitrate, triamcinolone acetonide and benzoic acid in a ternary mixture.Methods:Separation was conducted on Mediterranea C18 (150mm x 4.6mm, 5μm) column using methanol: 50 mM potassium dihydrogen phosphate buffer (pH 2.60±1), (70:30, v/v) as a mobile phase at ambient temperature. Isocratic flow rate at 1 ml/min was used and UV detection was carried out at 230 nm. The Linearity, accuracy and precision of the developed method investigated as per ICH guidelines.Results:Good separation of two drugs, benzoic acid as preservative and excipients of dosage form was achieved with acceptable retention times (< 8 min). Validation parameters tested including linearity, accuracy and precision were found to be satisfactory over the concentration range (10-200 µg/ml) for econazole nitrate, (1-20 µg/ml) for triamcinolone acetonide and (2-40 μg/ml) for benzoic acid.Conclusion:The proposed method showed good separation and demonstrated adequate specificity, robustness and accuracy for the quantification of the tested drugs in laboratory prepared mixtures and in pharmaceutical preparations.
Tissue Distribution of Engeletin in Mice by UPLC-MS/MS
Authors: Ye Weijian , Lin Chongliang , Lin Guanyang , Chen Ruijie , Sun Wei , Wang Shuanghu , Wang Xianqin , Zhou Yunfang 
Published: May 2018

Introduction:
Engeletin is the main active component in the engelhardia leaf that promotes
circulation and removes stasis, and has hypoglycemic, hypolipidemic, and anti-inflammatory actions.
The aim of this study was to develop an ultra-performance liquid chromatography- tandem mass spectrometry
method to detect engeletin in plasma and tissues and investigate its absorption, distribution,
and mechanism in mice, which could provide very useful information for its pharmacological effect in
vivo.

Materials and Methods:
Twenty-five mice were intraperitoneally injected with 20 mg/kg engeletin, and
five mice were sacrificed using 4% chloral hydrate 0.25, 0.5, 2, 4, and 6 h later. The tissues (brain, kidney,
heart, liver, spleen, and lung) and blood were collected. Acetonitrile precipitation was applied to
remove protein and further process the mouse plasma and tissue homogenate samples. Multiple reactions
monitoring mode in negative mode was used to quantify the engeletin.

Results and Conclusion:
Linearity of engeletin in plasma and tissues was good (R2 > 0.995), within the
range of 2-2,000 ng/mL in plasma and 2-2,000 ng/g in tissues, and the lower limit of quantitation was 2
ng/mL in plasma and 2 ng/g in tissues. Inter-day precision of engeletin in plasma or tissues (brain, kidney,
heart, liver, spleen, and lung) was < 14%, and intra-day precision was < 15%. After the mice were
intraperitoneally injected with engeletin (20 mg/kg), the distribution in kidney and liver was the highest,
followed by blood, spleen, lung, heart, and brain. Engeletin concentration in the brain was low, suggesting
that engeletin can penetrate through the blood brain barrier, which could also help with engeletin
investigations of the brain.
Preparation and Evaluation of Quercetin-Loaded MPEG-PLA Nanoparticles
Authors: Onishi Hiraku , Nakamura Masashi , Sasatsu Masanaho 
Published: May 2018

Background:
Quercetin (QE) is one of the flavonoids with various biological functions
such as anti-oxidation, anti-inflammatory and antitumor. However, the low aqueous solubility and
short half-life in the body reduce its in vivo efficacy. Therefore, the appropriate delivery techniques
to solve those problems have drawn much attention. In the present study, methoxypolyethylene glycol-
poly-DL-lactic acid (MPEG-PLA) nanoparticles loaded with quercetin (QE), called NP, were
prepared, and their antitumor characteristics were investigated in vitro and in vivo.

Method:
NPs were produced by evaporating organic solvent from the organic solvent-water mixture
in four formulations. The particle characteristics and in vitro release were examined for the obtained
preparations (NP1 – NP4). The antitumor features were investigated in vivo with different administration
schedules using mice inoculated subcutaneously with murine Sarcoma 180. In addition, the
efficacy of co-administration of NP with a strong antitumor chemotherapeutic agent, irinotecan hydrochloride
(CPT-11), was examined. Biodistribution studies were performed using the same animal
models.

Result:
The NP with the higher drug content (0.58 % (w/w)) and gradual release profile, Preparation
NP4, were chosen and used as NP in the in vivo studies. NP suppressed tumor growth better than QE
solution in various dosing schedules (total dose = 2 mg/kg). In the combination therapy with CPT-11,
NP exhibited antitumor efficacy in a nearly additive manner. No decrease in body weight observed
with any administration. NP markedly enhanced the systemic distribution and tumor localization.

Conclusion:
These results indicated that the present NP should promote the efficacy of QE, and
might have useful therapeutic potential in the treatment of solid tumors.
Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives
Authors: Banday Abid H. , Shameem Shameem A. , Banday Javid A. , Ganaie Bashir A. 
Published: May 2018

Background:
The potential of steroids for development into lead pharmacological molecules lies in
the regulation of a variety of biological processes by these molecules and also because of these being a fundamental
class of signaling molecules. Steroid based scaffolds have been extensively used as active pharmaceutical
agents for the treatment of various diseases including the deadly disease of cancer which despite the recent
advances in the early diagnosis, prevention and therapy, remains a clinical challenge affecting millions of people
world over and is one of the leading causes of death. It thus warrants the development of new drugs against this
dreadful disease through exploitation of emerging molecularly defined targets.

Methods:
The present study explores the effect of novel steroidal pyrazolines as presumed inhibitors of 5α-
reductase (5AR) and 17α-hydroxylase-C17,20-lyase as a target for treatment of prostate cancer. A series of 1,5-
diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis
of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5-
disubstituted pyrazolinyl pregnenolones is the heterocyclization of bezylidine derivatives (3) in presence of
phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization
to generate the stable pyrazoline derivatives.

Results:
All the synthesised D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were screened
for prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst
all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found
to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase
inhibitory activities.

Conclusion:
A series of D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were synthesized
and screened for their prostate cancer cell inhibitory, 5a-reductase and 17α-hydroxylase-C17,20-lyase inhibitory
activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g
and 5l were found to be the most active whereas compounds 5g and 5h were found to have moderate 17α-
hydroxylase-C17,20-lyase inhibitory activities.
Vitamin D’s Molecular Action Mechanism in Attention-Deficit/ Hyperactivity Disorder: A Review of Evidence
Authors: Saedisomeolia Ahmad , Samadi Mahsa , Gholami Fatemeh , Seyedi Marzieh , Effatpanah Mohammad , Hashemi Rezvan , Abdolahi Mina , Honarvar Niyaz Mohammadzadeh 
Published: May 2018

Background & Objective:
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous
disorder characterized by hyperactivity, impulsivity and inattention. Children with ADHD have
challenges with learning, behavior and psychosocial adjustments, sometimes retained into adulthood.
The exact etiology of ADHD is unknown, and the pathophysiology of this disease is complex. Several
hypotheses have been raised regarding ADHD pathogenesis, including serotonergic and catecholaminergic
signalling pathway dysfunction, neurotropic-related factors, oxidative stress, or neuroinflammation.

Vitamin D has an important protective effect against inflammation, oxidative stress and certain neurotrophic
factors and neurotransmitter, as well as facilitating dopaminergic and serotonergic functions.
Vitamin D levels in children with ADHD are lower than in healthy children, and thus may be involved
in the pathogenesis of ADHD. These observations, therefore, confirm the neuroprotective role of vitamin
D through multiple molecular mechanisms and can be considered as a promising target in understanding
ADHD pathology.

Conclusion:
In this context, the present study reviews the molecular pathways of vitamin D in ADHD
patients.
AMELIORATION OF GENTAMICIN-INDUCED RENAL DAMAGE IN RATS BY ETHANOL EXTRACT OF THE WHOLE PLANT BIOPHYTUM SENSITIVUM (LINN.) DC
Authors: R. Abhirama B. , R Shanmuga Sundaram , A Raju 
Published: May 2018

Objective: Present study was undertaken to investigate the nephroprotective activity of whole plant ethanol extract of Biophytum sensitivum Linn. DC (B. sensitivum; EEBS) on gentamicin induced-nephrotoxicity in Wistar albino rats.Methods: Animals were divided into five groups, containing six animals in each. Gentamicin (GM) 100 mg/kg/d; i. p., was given to all groups except normal control to induce nephrotoxicity for a period of 8 d in rats. Animals in Group I served as control and Group II as GM-treated or nephrotoxic control. Group III received standard quercetin (50 mg/kg; p. o.); group IV received EEBS (250 mg/kg; p. o.) and group V received EEBS (500 mg/kg; p. o.), for 8 d. Several renal functional tests and injury markers such as a change in body weight, water intake, urine volume and pH, urinary levels of total protein, albumin, sodium, potassium, calcium and magnesium were measured. Different hematological parameters including, red blood cells (RBC), hemoglobin (Hb), packed cell volume (PCV), mean corpuscular haemoglobin (MCH), white blood corpuscles (WBC), lymphocyte, monocyte, polymorphs and eosinophil were also analyzed.Results: The results revealed that co-administration of EEBS at 250 and 500 mg/kg significantly reduced the urinary excretion of total protein (4.05±0.04, 3.53±0.05 g/dl), albumin (0.81±0.08, 0.71±0.00 g/dl), calcium (8.05±0.05, 7.81±0.06 mg/dl) and magnesium (0.79±0.05, 0.77±0.06 mg/dl) respectively. EEBS treatment in group IV and V animals produced a significant increase in body weight (2.58±0.17, 2.52±0.22 g), water intake (17.35±0.82, 17.87±0.86 ml/24 h) urine output (7.24±0.15, 7.88±0.08 ml/24 h), compared to animals in group II. Co-therapy with both doses of extracts also showed significant increase in RBC (6.85±0.31, 7.10±0.43 million/mm3) Hb (13.96±0.21, 13.83±0.31 g/dl), MCH (20.45±0.49, 20.67±0.51 pg) and PCV (38.29±0.42, 38.53±0.20%) levels, whereas WBC (8.24±0.21, 8.15±0.10 1X103/mm3) and polymorphs (14.19±0.20, 14.05±0.11%) levels were found to be significantly reduced respectively in animals than those in toxic control group.Conclusion: This study substantiated and confirmed the ethnomedical usefulness of B. sensitivum as a nephroprotective and antioxidant agent.
Class III malocclusion and bilateral cross-bite in an adult patient treated with miniscrew-assisted rapid palatal expander and aligners
Authors: Lombardo Luca , Carlucci Antonella , Maino Bortolo Giuliano , Colonna Anna , Paoletto Emanuele , Siciliani Giuseppe 
Published: May 2018

ABSTRACT
This case report describes the use of a miniscrew-assisted rapid palatal expander and aligners to correct bilateral cross-bite and crowding in an adult patient with a Class III skeletal pattern. A digitally designed surgical guide was three-dimensionally printed and used to accurately insert four miniscrews into the palate; these were employed to anchor a novel miniscrew-assisted rapid palatal expander appliance without any dental anchorage. Cone-beam computed tomograms before and after miniscrew-assisted rapid palatal expander treatment demonstrated the orthopedic expansion of the maxilla without dental tipping. The patient was then fitted with aligners to correct crowding and malocclusion. This case report demonstrates the successful treatment of an adult patient with a narrow maxilla and bilateral cross-bite using a nonsurgical, conservative treatment.
Metabolic Syndrome and Neurocognition Among Diverse Middle-Aged and Older Hispanics/Latinos: HCHS/SOL Results
Authors: González Hector M. , Tarraf Wassim , Vásquez Priscilla , Sanderlin Ashley H. , Rosenberg Natalya I. , Davis Sonia , Rodríguez Carlos J. , Gallo Linda C. , Thyagarajan Bharat , Daviglus Martha , Khambaty Tasneem , Cai Jianwen , Schneiderman Neil 
Published: May 2018

OBJECTIVEHispanics/Latinos have the highest risks for metabolic syndrome (MetS) in the U.S. and are also at increased risk for Alzheimer disease. In this study, we examined associations among neurocognitive function, MetS, and inflammation among diverse middle-aged and older Hispanics/Latinos.RESEARCH DESIGN AND METHODSCross-sectional data (2008–2011) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analyzed to examine associations between neurocognition and MetS among diverse Hispanics/Latinos (N = 9,136; aged 45–74 years).RESULTSMetS status was associated with lower global neurocognition, mental status, verbal learning and memory, verbal fluency, and executive function. Age significantly modified the associations between MetS and learning and memory measures. Significant associations between MetS and neurocognition were observed among middle-aged Hispanics/Latinos, and all associations remained robust to additional covariates adjustment.CONCLUSIONSWe found that MetS was associated with lower neurocognitive function, particularly in midlife. Our findings support and extend current hypotheses that midlife may be a particularly vulnerable developmental period for unhealthy neurocognitive aging.