bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression
Authors: Carta Sonia , Silvestri Michela , Rossi Giovanni A
Published: May 2013

Background

Recurrent respiratory infections are one of the most important causes of morbidity in childhood. When immune functions are still largely immature, the airway epithelium plays a primary defensive role since, besides providing a physical barrier, it is also involved in the innate and the adaptive immune responses. A study was therefore designed to evaluate in vitro whether pidotimod, a synthetic dipeptide able to stimulate the inflammatory and immune effector cells, could activate bronchial epithelial cell functions involved in response to infections.

Methods

BEAS-2B cell line (human bronchial epithelial cells infected with a replication-defective Adenovirus 12-SV40 virus hybrid) were cultured in the presence of pidotimod, with or without tumor necrosis factor (TNF)-α or zymosan to assess: a) intercellular adhesion molecule (ICAM)-1 expression, by flow cytometry; b) toll-like receptor (TLR)-2 expression and production, by immunofluorescence flow cytometry and western blotting; d) interleukin (IL)-8 release, by enzyme-linked immunosorbent assay (ELISA); e) activated extracellular-signal-regulated kinase (ERK1/2) phosphorylation and nuclear factor-kappa B (NF-kB) activation, by western blotting.

Results

The constitutive expression of ICAM-1 and IL-8 release were significant up-regulated by TNF-α (ICAM-1) and by TNF-α and zymosan (IL-8), but not by pidotimod. In contrast, an increased TLR-2 expression was found after exposure to pidotimod 10 and 100 μg/ml (p < 0.05) and to the association pidotimod 100 μg/ml + TNF-α (p < 0.05). Western blot analysis substantiated that the constitutive TLR-2 expression was significantly increased after exposure to all the stimuli. Finally, while a remarkable inhibition of TNF-α -induced ERK1/2 phosphorylation was observed in the presence of pidotimod, both TNF-α and pidotimod were effective in inducing NF-kB protein expression in the cytoplasm and its nuclear translocation.

Conclusion

Through different effects on ERK1/2 and NF-kB, pidotimod was able to increase the expression of TLR-2 proteins, surface molecules involved in the initiation of the innate response to infectious stimuli. The lack of effect on ICAM-1 expression, the receptor for rhinovirus, and on IL-8 release, the potent chemotactic factor for neutrophils (that are already present in sites of infection), may represent protective functions. If confirmed in vivo, these activities may, at least in part, clarify the mechanism of action of this molecule at airway level.
Alterations in histopathological features and brain acetylcholinesterase activity in stinging catfish Heteropneustes fossilis exposed to polluted river water
Authors: Rakhi Sharmin Ferdewsi , Reza Abdul Hakim Mohammad Mohsinul , Hossen Mohammad Shafaet , Hossain Zakir
Published: May 2013

Responses of stinging catfish (Heteropneustes fossilis) to pollution were studied in three freshwater rivers, namely Buriganga, Turag, and Shitalakkhya (Dhaka, Bangladesh), which are potentially affected by anthropogenic pollution originating from industrial and sewage dumping. Partial parameters about water quality (temperature, dissolved oxygen, and pH) and seasonal plankton fluctuation were recorded at wet and dry seasons. Histopathology and acetylcholinesterase (AChE) activity were used as biomarkers to assess water toxic effects in 7-and 10-day exposures of H. fossilis to three rivers waters, respectively. The lowest level of dissolved oxygen was recorded as 0.7 ± 0.1 mg/l, and the lowest count of plankton genera was 21 at lean period. Furthermore, the 7-day exposure of fish to polluted water abruptly altered the normal structure of various organs. Major structural damages were partial and total epidermal loss, dermis and muscle separation, melanin pigment and vacuole in skin muscle; missing of lamellae, clubbing, fungal granuloma, hyperplasia and hemorrhage in gills; hyperplasia, hemorrhage, pyknosis, vacuole, necrosis, nuclear alteration, fatty degeneration, lipid droplets in liver; degenerating glomerular and tubule, hemorrhage, pyknosis and vacuole in kidneys; and scattered spermatozoa and prominent interstitial space in the testis. After subsequent exposure to polluted water, a significant (P < 0.05) inhibition of AChE activity in the fish brain was observed with the following order of potency: 102.00 ± 5.00 nmol/min/mg protein (Turag) ≥ 104.00 ± 5.00 nmol/min/mg protein (Buriganga) > 130.67 ± 3.51 nmol/min/mg protein (Shitalakkhya). This study confirmed the utility of biomarkers in biomonitoring studies and reflected the potential hazards of pollution to aquatic biota.
Peripheral nervous system insulin resistance in ob/ob mice
Authors: Grote Caleb W , Groover Anna L , Ryals Janelle M , Geiger Paige C , Feldman Eva L , Wright Douglas E
Published: May 2013

Background

A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis.

Results

The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons.

Conclusions

These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy.
Incremental development & revolutions of E-learning software systems in education sector: a case study approach
Authors: Gupta Varun , Chauhan Durg Singh , Dutta Kamlesh
Published: May 2013

Advancement in the area of software engineering, mobile computing together with web technologies have paved way for myriad range of applications, including good quality E-learning software’s, delivering online classes in real time to unlimited number of students across the world, on a personalized E-learning space for every student. These E-learning software systems have virtually made the whole world as a single campus education hub. However, development of these software’s has been a challenge for industry, as the requirement of various stakeholders–learner, educator, institutional management, accreditation bodies, has to be handled in the software effectively. Software systems developed for E-learning applications should implement all the requirements of its diverse stakeholders and must be delivered well in time. Delays, incomplete software and faulty modules could be a big failure for educational institute. To be able to deliver the software within deadline, software’s are delivered in increments. In order to support incremental delivery, paper proposes a new requirement prioritization method that selects those requirements for implementation that are essentially required by stakeholders and has a lower regression count associated with them, thereby reducing regression testing effort.

This paper reports the advantages reaped from E-learning software project of “Virtual Classroom” employed in teaching “Multimedia Technologies” course to undergraduate students of sixth semester. Total 50 students, enrolled under both distance education and full time education (25 in each category), were asked a set of questions. Results indicate that E-learning system would bring revolution in the field of education, whether study program is full time, part time or a distance education program. Students found augmenting classroom teaching with the use of E-learning software systems as an enriching experience.
Chaperone Properties of Pdia3 Participate in Rapid Membrane Actions of 1α,25-Dihydroxyvitamin D3
Authors: Chen Jiaxuan , Lobachev Kirill S. , Grindel Brian J. , Farach-Carson Mary C. , Hyzy Sharon L. , El-Baradie Khairat B. , Olivares-Navarrete Rene , Doroudi Maryam , Boyan Barbara D. , Schwartz Zvi
Published: May 2013

Protein disulfide isomerase family A, member 3 (Pdia3) mediates many of the plasma membrane (PM)-associated rapid responses to 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). It is not well understood how Pdia3, which is an endoplasmic reticulum (ER) chaperone, functions as a PM receptor for 1α,25(OH)2D3. We mutated 3 amino acids (K214 and R282 in the calreticulin interaction site and C406 in the isomerase catalytic site), which are important for Pdia3's ER chaperone function, and examined their role in responses to 1α,25(OH)2D3. Pdia3 constructs with and without the ER retention signal KDEL were used to investigate the PM requirement for Pdia3. Finally, we determined whether palmitoylation and/or myristoylation were required for Pdia3-mediated responses to 1α,25(OH)2D3. Overexpressing the Pdia3 R282A mutant in MC3T3-E1 cells increased PM phospholipase A2-activating protein, Rous sarcoma oncogene (c-Src), and caveolin-1 but blocked increases in 1α,25(OH)2D3-stimulated protein kinase C (PKC) seen in cells overexpressing wild-type Pdia3 (Pdia3Ovr cells). Cells overexpressing Pdia3 with K214A and C406S mutations had PKC activity comparable to untreated controls, indicating that the native response to 1α,25(OH)2D3 also was blocked. Overexpressing Pdia3[−KDEL] increased PM localization and augmented baseline PKC, but the stimulatory effect of 1α,25(OH)2D3 was comparable to that seen in wild-type cultures. In contrast, 1α,25(OH)2D3 increased prostaglandin E2 in Pdia3[±KDEL] cells. Although neither palmitoylation nor myristoylation was required for PM association of Pdia3, myristoylation was needed for PKC activation. These data indicate that both the chaperone functional domains and the subcellular location of Pdia3 control rapid membrane responses to 1α,25(OH)2D3.
Preventing p38 MAPK-Mediated MafA Degradation Ameliorates β-Cell Dysfunction under Oxidative Stress
Authors: El Khattabi Ilham , Sharma Arun
Published: May 2013

The reduction in the expression of glucose-responsive insulin gene transcription factor MafA accompanies the development of β-cell dysfunction under oxidative stress/diabetic milieu. Humans with type 2 diabetes have reduced MafA expression, and thus preventing this reduction could overcome β-cell dysfunction and diabetes. We previously showed that p38 MAPK, but not glycogen synthase kinase 3 (GSK3), is a major regulator of MafA degradation under oxidative stress. Here, we examined the mechanisms of this degradation and whether preventing MafA degradation under oxidative stress will overcome β-cell dysfunction. We show that under oxidative and nonoxidative conditions p38 MAPK directly binds to MafA and triggers MafA degradation via ubiquitin proteasomal pathway. However, unlike nonoxidative conditions, MafA degradation under oxidative stress depended on p38 MAPK-mediated phosphorylation at threonine (T) 134, and not T57. Furthermore the expression of alanine (A) 134-MafA, but not A57-MafA, reduced the oxidative stress-mediated loss of glucose-stimulated insulin secretion, which was independent of p38 MAPK action on protein kinase D, a regulator of insulin secretion. Interestingly, the expression of proteasomal activator PA28γ that degrades GSK3-phosphorylated (including T57) MafA was reduced under oxidative stress, explaining the dominance of p38 MAPK over the GSK3 pathway in regulating MafA stability under oxidative stress. These results identify two distinct pathways mediating p38 MAPK-dependent MafA degradation under oxidative and nonoxidative conditions and show that inhibiting MafA degradation under oxidative stress ameliorates β-cell dysfunction and could lead to novel therapies for diabetes.
Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila
Authors: Ducuing Antoine , Mollereau Bertrand , Axelrod Jeffrey D. , Vincent Stephane
Published: May 2013

How morphogen gradients are shaped is a major question in developmental biology, but remains poorly understood. Hedgehog (Hh) is a locally secreted ligand that reaches cells at a distance and acts as a morphogen to pattern the Drosophila wing and the vertebrate neural tube. The proper patterning of both structures relies on the precise control over the slope of Hh activity gradient. A number of hypotheses have been proposed to explain Hh movement and hence graded activity of Hh. A crux to all these models is that the covalent binding of cholesterol to Hh N-terminus is essential to achieve the correct slope of the activity gradient. Still, the behavior of cholesterol-free Hh (Hh-N) remains controversial: cholesterol has been shown to either increase or restrict Hh range depending on the experimental setting. Here, in fly embryos and wing imaginal discs, we show that cholesterol-free Hh diffuses at a long-range. This unrestricted diffusion of cholesterol-free Hh leads to an absence of gradient while Hh signaling strength remains uncompromised. These data support a model where cholesterol addition restricts Hh diffusion and can transform a leveled signaling activity into a gradient. In addition, our data indicate that the receptor Patched is not able to sequester cholesterol-free Hh. We propose that a morphogen gradient does not necessarily stem from the active transfer of a poorly diffusing molecule, but can be achieved by the restriction of a highly diffusible ligand.
Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian
Authors: Kanska Justyna , Frank Uri
Published: May 2013

Nanos is a pan-metazoan germline marker, important for germ cell development and maintenance. In flies, Nanos also acts in posterior and neural development, but these functions have not been demonstrated experimentally in other animals. Using the cnidarian Hydractinia we uncover novel roles for Nanos in neural cell fate determination. Ectopic expression of Nanos2 increased the numbers of embryonic stinging cell progenitors, but decreased the numbers of neurons. Downregulation of Nanos2 had the opposite effect. Furthermore, Nanos2 blocked maturation of committed, post-mitotic nematoblasts. Hence, Nanos2 acts as a switch between two differentiation pathways, increasing the numbers of nematoblasts at the expense of neuroblasts, but preventing nematocyte maturation. Nanos2 ectopic expression also caused patterning defects, but these were not associated with deregulation of Wnt signaling, showing that the basic anterior-posterior polarity remained intact, and suggesting that numerical imbalance between nematocytes and neurons may have caused these defects, affecting axial patterning only indirectly. We propose that Nanos' functions in germ cells and neural development are evolutionarily conserved, but its role in posterior patterning is an insect or arthropod innovation.
Heart rate and estimated energy expenditure of flapping and gliding in black-browed albatrosses
Authors: Sakamoto Kentaro Q. , Takahashi Akinori , Iwata Takashi , Yamamoto Takashi , Yamamoto Maki , Trathan Philip N.
Published: May 2013

Albatrosses are known to expend only a small amount of energy during flight. The low energy cost of albatross flight has been attributed to energy-efficient gliding (soaring) with sporadic flapping, although little is known about how much time and energy albatrosses expend in flapping versus gliding during cruising flight. Here, we examined the heart rates (used as an instantaneous index of energy expenditure) and flapping activities of free-ranging black-browed albatrosses (Thalassarche melanophrys) to estimate the energy cost of flapping as well as time spent in flapping activities. The heart rate of albatrosses during flight (144 beats min-1) was similar to that while sitting on the water (150 beats min-1). In contrast, heart rate was much higher during takeoff and landing (ca. 200 beats min-1). Heart rate during cruising flight was linearly correlated with the number of wing flaps per minute, suggesting an extra energy burden of flapping. Albatrosses expend only 4.6% ± 1.4% of their time in flapping during cruising flight, which was significantly lower than those during and shortly after takeoff (9.8% ± 3.5%). Flapping activity, which amounted to just 4.6% of the time in flight, accounted for 13.3% of the total energy expenditure during cruising flight. These results support the idea that albatrosses achieve energy-efficient flight by reducing the time spent in flapping activity, which is associated with high energy expenditure.
Aluminum exposure impacts brain plasticity and behavior in Atlantic salmon (Salmo salar)
Authors: Grassie Cairsty , Braithwaite Victoria A. , Nilsson Jonatan , Nilsen Tom O. , Teien Hans-Christian , Handeland Sigurd O. , Stefansson Sigurd O. , Tronci Valentina , Gorissen Marnix , Flik Gert , Ebbesson Lars O. E.
Published: May 2013

Aluminum (Al) toxicity occurs frequently in natural aquatic ecosystems as a result of acid deposition and natural weathering processes. Detrimental effects of Al toxicity on aquatic organisms are well known and can have consequences for survival. Fish exposed to Al in low pH waters will experience physiological and neuroendocrine changes that disrupt homeostasis and alter behavior. To investigate the effects of Al exposure to both brain and behavior, Atlantic salmon (Salmo salar) kept in water treated with Al (pH 5.7, 0.37±0.04 µmol 1-1 of Al) for 2 weeks were compared to fish kept in a control condition (pH 6.7, <0.04 µmol 1-1 of Al). Fish exposed to Al and acidic conditions had increased Al accumulation in the gills and decreased gill Na+, K+-ATPase activity, which impaired osmoreguatory capacity and caused physiological stress, indicated by elevated plasma cortisol and glucose levels. Here we show for the first time that exposure to Al in acidic conditions also impaired learning performance in a maze task. Al toxicity reduced the expression of NeuroD1 transcript levels in the forebrain of exposed fish. As in mammals, these data show that exposure to chronic stress, such as acidified Al, can reduce neural plasticity during behavioral challenges in salmon, and may impair coping ability to new environments.
The effects of caudal fin loss and regeneration on the swimming performance of three cyprinid fish with different swimming capacities
Authors: Fu Cheng , Cao Zhen-Dong , Fu Shi-Jian
Published: May 2013

In nature, the caudal fins of fish species are frequently lost to some extent by aggressive behaviour, predation and diseases. To test whether the swimming performance of fish with different swimming capacities would be differentially affected due to caudal fin loss and regeneration, we investigated the critical swimming speed (Ucrit), the swimming metabolic rate (MO2), the tail beat frequency (TBF) and the tail beat amplitude (TBA) after caudal fin loss and regeneration (20 days) in juveniles of three cyprinid fish species: the qingbo (Spinibarbus sinensis) (strong swimmer), the common carp (Cyprinus carpio) (intermediate) and the goldfish (Carassius auratus) (poor swimmer). The Ucrits of the caudal-fin-lost qingbo, common carp and goldfish were 49%, 32% and 35% significantly lower than those of the control groups, respectively. The maximum tail beat amplitude (TBAmax) (all three fishes), the maximum tail beat frequency (TBFmax) (only the common carp and the goldfish) and/or the active metabolic rate (MO2active) (only the common carp) of the caudal-fin-lost fish were significantly higher than those of the control groups. After 20 days of recovery, the caudal fins recovered to 41%, 47% and 24% of those of the control groups for the qingbo, the common carp and the goldfish, respectively. However, the Ucrit values of the fin-regenerated qingbo, common carp and goldfish recovered to 86%, 91% and 95% of those of the control group, respectively. The caudal-fin-regenerated qingbo and common carp showed a significantly higher TBAmax and TBFmax, respectively, compared with those of the control groups. The qingbo had a higher TBFmax but a lower TBAmax than the common carp and the goldfish, which suggested that a strong swimmer may maintain swimming speed primarily by maintaining a greater TBFmax, for which the caudal fin plays a more important role during swimming, than a poor swimmer. The MO2active of fish (common carp) with a redundant respiratory capacity could increase due to caudal fin loss to meet the increase in energy expenditure required by an increase in TBFmax. In addition, the sustain swimming performance may not be the only selective pressure acting on caudal fin size in the qingbo, the common carp and the goldfish and the present caudal fin size of these three fish species may be a trade-off between sustain swimming performance and other factors (e. g. sexual selection; escape responses).
Modulation of Rh glycoproteins, ammonia excretion and Na+ fluxes in three freshwater teleosts when exposed chronically to high environmental ammonia
Authors: Sinha Amit K. , Liew Hon J. , Nawata C. Michele , Blust Ronny , Wood Chris M. , De Boeck Gudrun
Published: May 2013

We investigated relationships among branchial unidirectional Na+ fluxes, ammonia excretion, urea excretion, plasma ammonia, plasma cortisol, and gill transporter expression and function in three freshwater fish differing in their sensitivity to high environmental ammonia (HEA). The highly ammonia-sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less ammonia-sensitive cyprinid Cyprinus carpio (common carp) and the highly ammonia-resistant cyprinid Carassius auratus (goldfish) were exposed chronically (12 h to 168 h) to 1 mM ammonia (as NH4HCO3; pH 7.9). During HEA, carp and goldfish elevated ammonia excretion (Jamm) and Na+ influx rates (JNain) while trout experienced higher plasma ammonia (Tamm) and were only able to restore control rates of Jamm and JNain. All three species exhibited increases in Na+ efflux rate (JNaout). At the molecular level, there was evidence for activation of a "Na+/NH4+ exchange metabolon” likely in response to elevated plasma cortisol and Tamm, though surprisingly, some compensatory responses preceded molecular responses in all three species. Rhbg, Rhcg (Rhcg-a and Rhcg-b), H+-ATPase (V-type, B-subunit) and Na+/K+-ATPase (NKA) mRNA expressions were up-regulated in goldfish, Rhcg-a and NKA in carp, and Rhcg2, NHE-2 (Na+/H+ exchanger) and H+-ATPase in trout. Branchial H+-ATPase activity was elevated in goldfish and trout, and NKA activity in goldfish and carp, but NKA did not appear to function preferentially as a Na+/NH4+-ATPase in any species. Goldfish alone increased urea excretion rate during HEA, in concert with elevated urea transporter mRNA expression in gills. Overall, goldfish showed more effective compensatory responses towards HEA than carp, while trout were least effective.
A fluorescence study of the solute–solvent interactions of
aminochalcones in a room-temperature ionic liquid
Authors: Santhosh Kotni , Grandhi G. Krishnamurthy , Ghosh Snigdha , Samanta Anunay
Published: May 2013

Unlike most other electron donor–acceptor (EDA) molecules, aminochalcones exhibit
unusual solvent polarity-dependent fluorescence behavior. The photophysical
behavior of two aminochalcones, namely, 4-aminochalcone (AC) and
4-dimethylaminochalcone (DMAC), has been studied in a viscous room-temperature
ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate,
[bmim][PF6], by steady-state and time-resolved fluorescence
techniques. The observation of a single emission band in viscous IL, which is
similar to the one observed in less viscous polar conventional solvents,
suggests no twisting is necessary for the formation of the charge-transfer state
from which the emission of aminochalcones originates. The fluorescence decay
profiles, solvation dynamics, and excitation-wavelength-dependent emission
behavior of AC are found to be quite different from those of DMAC in the IL. The
observed difference is attributed to specific H-bonding interaction between AC
and [bmim][PF6].
Effects of medical therapies for acromegaly on glucose metabolism
Authors: Urbani C , Sardella C , Calevro A , Rossi G , Scattina I , Lombardi M , Lupi I , Manetti L , Martino E , Bogazzi F
Published: May 2013

Objective

Abnormalities of glucose metabolism are common findings of acromegaly. However, robust evidence on whether therapy with somatostatin analogs (SSAs) or pegvisomant (PEG) differently affects glucose metabolism is lacking. The purpose of this study was to evaluate the effects of therapy with SSAs, PEG, or their combination on glucose metabolism in a large series of acromegalic patients.

Design

This was a historical–prospective study. Among 50 consecutive acromegalic patients under SSA therapy, acromegaly in 19 patients was controlled. PEG used in combination with SSA therapy allowed the control of acromegaly in the remaining 31 patients and was then continued as monotherapy in 18 patients.

Methods

The following parameters were evaluated at the diagnosis of acromegaly and during different treatments: fasting plasma glucose (FPG) and insulin concentrations, insulin sensitivity (QUICK-I), homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Comparison was made using analysis for paired data.

Results

Insulin resistance improved when acromegaly was controlled with therapy with SSAs, PEG, or SSA+PEG. However, FPG concentrations were higher during SSA therapy (alone or combined with PEG) than at the diagnosis of acromegaly, even when corrected for disease activity, whereas they were reduced during PEG therapy. Mean glucose concentrations during the OGTT were higher in patients receiving SSA therapy than in those receiving PEG therapy. In addition, the prevalence of diabetes or impaired glucose tolerance was higher during SSA therapy than at diagnosis or during PEG therapy and was not influenced by disease control.

Conclusions

Medical therapies for acromegaly reduce insulin resistance and increase insulin sensitivity; on the contrary, glucose indexes may be differently affected by SSA or PEG therapy.
Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians
Authors: Varshney Shweta , Bhadada Sanjay Kumar , Saikia Uma Nahar , Sachdeva Naresh , Behera Arunanshu , Arya Ashutosh Kumar , Sharma Sadhna , Bhansali Anil , Mithal Ambrish , Rao Sudhaker D
Published: May 2013

Background

To explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).

Materials and methods

Forty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (n=3) or from euthyroid patients without PHPT during thyroid surgery (n=7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR.

Results

Immunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, bothVDRandCASRmRNAs were reduced by 0.36- and 0.45-fold change (P<0.001) andCD1andPTHmRNAs were increased by 9.4- and 17.4-fold change respectively (P<0.001) in adenomatous parathyroid tissue.PTHmRNA correlated with plasma PTH (r=0.864;P<0.001), but not with adenoma weight, whileCD1mRNA correlated with adenoma weight (r=0.715;P<0.001). There were no correlations betweenVDRandCASRmRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases inVDRandCASRmRNA expressions and the increases inPTHandCD1mRNA expressions.

Conclusions

The expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition,CD1expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.
Mortality outcomes of different sulphonylurea drugs: the results of a 14-year cohort study of type 2 diabetic patients
Authors: Bo Simona , Castiglione Anna , Ghigo Ezio , Gentile Luigi , Durazzo Marilena , Cavallo-Perin Paolo , Ciccone Giovannino
Published: May 2013

Objective

Available data about mortality of type 2 diabetic patients treated with different sulphonylureas are scarce and contradictory.

Design

We evaluated the associations between all-cause and cause-specific mortality and treatments with different sulphonylureas in a retrospective cohort of type 2 diabetic patients from a diabetes clinic.

Methods

All 1277 patients treated with sulphonylureas during 1996–1997 were enrolled: 159 patients were treated with tolbutamide, 977 glibenclamide and 141 gliclazide. The baseline data (centralised laboratory parameters, anthropometric data and presence of chronic complications) were abstracted from the clinical records. Information on vital status was collected from demographic files after 14-year follow-up. Adjusted hazard ratios (HR) were estimated with Cox (all-cause mortality) or Fine and Gray models (cause-specific mortality), including several potential confounders.

Results

Five hundred and fifty-six patients died during the follow-up: 262 from cardiovascular causes, 158 from cancer and 136 from other causes. When compared with the glibenclamide users, the gliclazide and tolbutamide users showed a significantly lower cancer mortality (HR=0.30; 95% CI 0.16–0.55, and HR=0.48; 95% CI 0.29–0.79 respectively). These results were strongly confirmed in the 555 patients on sulphonylurea monotherapy. None of the patients who were treated with gliclazide monotherapy died from cancer during the follow-up, and the patients on tolbutamide treatment exhibited a lower cancer mortality than the glibenclamide users (HR=0.40; 95% CI 0.22–0.71). Data did not change after stratification for the duration of sulphonylurea treatment from diabetes diagnosis to the study enrolment.

Conclusions

Cancer mortality was markedly reduced in the patients on gliclazide and tolbutamide treatment. These results suggest additional benefits for these drugs beyond their blood glucose-lowering effect and strongly advocate for further investigation.
DNA methylation in germ cell tumour aetiology: current understanding and outstanding questions
Authors: Cusack Martin , Scotting Paul
Published: May 2013

Germ cell tumours (GCTs) are a diverse group of neoplasms that can be histologically subclassified as either seminomatous or non-seminomatous. These two subtypes have distinct levels of differentiation and clinical characteristics, the non-seminomatous tumours being associated with poorer prognosis. In this article, we review how different patterns of aberrant DNA methylation relate to these subtypes. Aberrant DNA methylation is a hallmark of all human cancers, but particular subsets of cancers show unusually high frequencies of promoter region hypermethylation. Such a ‘methylator phenotype’ has been described in non-seminomatous tumours. We discuss the possible cause of distinct methylation profiles in GCTs and the potential of DNA methylation to provide new targets for therapy. We also consider how recent developments in our understanding of this epigenetic modification and the development of genome-wide technologies are shedding new light on the role of DNA methylation in cancer aetiology.
Frequency of non-motor symptoms in Peruvian patients with Parkinson's disease
Authors: Cosentino Carlos , Nuñez Yesenia , Torres Luis
Published: May 2013

Introduction: Non-motor symptoms in Parkinson's disease are often not well recognized in clinical practice. Non-motor symptoms questionnaire (NMSQuest) is a simple instrument that allows patients or caregivers to report non-motor symptoms in a practical manner. Objective: We attempted to determine the prevalence of non-motor symptoms in three hundred Parkinson's disease outpatients. Results: The mean total non-motor symptoms was 12.41, ranging from 0 to 27 of a maximum of 30. At least one was present in 99.3% of patients. A progressive increase in mean total score was observed across each 5-year interval. Depression domain scored the most “positive” answers while urinary and anxiety /memory were secondly and thirdly most prevalent respectively. Conclusion: The large number of patients included in this study allowed evaluation of the occurrence of non-motor symptoms in early and advanced disease in addition to the relationship of these kinds of symptoms with progression of disease.
Programmable valve represents an efficient and safe tool in the treatment of idiopathic normal-pressure hydrocephalus patients
Authors: Oliveira Matheus Fernandes de , Saad Felippe , Reis Rodolfo Casimiro , Rotta José Marcus , Pinto Fernando Campos Gomes
Published: May 2013

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait disturbance, dementia and /or urinary incontinence, dilation of the ventricular system and normal opening cerebrospinal fluid pressure. Shunt surgery is the standard treatment of iNHP. Diversions with programmable valves are recommended, once drainage pressure can be changed. However, well-defined protocols still lack guiding the steps to attain proper pressure for each patient. Methods: In our study, we reported the experience of shunting 24 patients with iNPH using Strata® (Medtronic) valve, following a protocol based on a positive Tap Test. Results: We observed clinical improvement in 20 patients and stability/worsening in 4 patients. Complications occurred in five patients, including one death. The results display improvement, and complications occurred at a lower rate than reported in other studies. Conclusions: The Strata® valve used in the proposed protocol represents an efficient and safe tool in the treatment of iNPH.
Stimulated jitter with concentric needle in 42 myasthenia gravis patients
Authors: Kouyoumdjian João Aris , Stålberg Erik
Published: May 2013

Objective: To estimate jitter parameters in myasthenia gravis in stimulated frontalis and extensor digitorum muscles using the concentric needle electrode. Methods: Forty-two confirmed myasthenia gravis patients, being 22 males (aged 45.6±17.2 years-old) were studied. Jitter was expressed as the mean consecutive difference (MCD). Results: MCD in extensor digitorum was 61.6 µs (abnormal in 85.7%) and in frontalis 57.3 µs (abnormal in 88.1%). Outliers represented 90.5% for extensor digitorum and 88.1% for frontalis. At least one jitter parameter was abnormal in 90.5% of the combined studies. Acetylcholine receptor antibody was abnormal in 85.7% of the cases. Conclusions: Stimulated jitter recordings measured from muscles using concentric needle electrode can be used for myasthenia gravis diagnosis with high sensitivity. Extensive normative studies are still lacking and, therefore, borderline findings should be judged with great caution.
Comparison of functional electrical stimulation associated with kinesiotherapy and kinesiotherapy alone in patients with hemiparesis during the subacute phase of ischemic cerebrovascular accident
Authors: Modesto Paulo Cesar , Pinto Fernando Campos Gomes
Published: May 2013

Objective: To compare the functional electrical stimulation associated with functional kinesiotherapy alone in patients after ischemic cerebrovascular accident. Methods: The study included 20 patients who were divided into two groups: Group I (GI): functional electrical stimulation plus functional kinesiotherapy and Group II (GII): functional kinesiotherapy. We evaluated active and passive range of motion, in knee flexion and extension muscle strength, activities of daily living and quality of life. The evaluations were conducted in the pretreatment period, after 10 sessions and after 20 physical therapy sessions. Results: There was a significant improvement in all variables studied for both groups. However, significant improvements for the sub-items functional capacity and social aspects were seen only in the patients treated with associated functional electrical stimulation and kinesiotherapy. Conclusion: Although both groups of patients improved with the treatment, the association of functional electrical stimulation and kinesiotherapy showed superiority in two quality of life items, in the sub-items functional capacity and social aspects.
Neurological contributions from William Osler
Authors: Pedroso José Luiz , Barsottini Orlando Graziani Povoas
Published: May 2013

William Osler was one of the most remarkable clinicians worldwide, and his teachings in medical practice remain until the present days. Although Osler had never considered himself a neurologist, he contributed with clinical and pathological descriptions of numerous neurological diseases. He performed more than 800 autopsies studies of the nervous system and published over 200 articles in the field of Neurology. In this article, we described the main neurological contributions from William Osler.
Structural aspects of blast furnace slag
Authors: Tiwary J. N. , Sarkar S. , Mishra B. , Mohanty U. K.
Published: May 2013

Interdependence of structure and viscosity of blast furnace slag is discussed based on the available literature. Emphasis is given to both, bridging tendency and network breaking/modifying tendency of the constituents. It is clearly pointed out that slag viscosity cannot be explained only by depolymerization through an increase in basicity, despite the fact that an increase in basicity of the slag, in general, lowers the viscosity of the slag by a process of generation of discrete anions containing simple chains and/or rings by causing depolymerization of the 3D silicate network.
Performance of large reinforced concrete columns under axial compression loads
Authors: Lee Tai-Kuang , Chen Cheng-Cheng , Hwa Ken , Pan Austin D. E.
Published: May 2013

Six sets of large-scale, square, reinforced concrete columns are tested under monotonically static axial compression loads. The primary variables are type of crosstie engagement, crosstie placement offset and type of hoop. The tests confirm that the crosstie hook engaging the hoop or engaging both the hoop and the longitudinal steel bars is better than just engaging the longitudinal steel bar. It is observed that the effect of not altering end for end along the longitudinal reinforcement is not significant to the efficiency of the crossties. Hoops composed of two overlapped L-shape ties, with a 135° hook at each end, in reinforced concrete columns gave acceptable performance, and it is convenient to facilitate the fabrication of reinforcing cages using that set-up. However, the effectiveness under cyclic loading needs further study.
Reddened seascapes: experimentally induced shifts in 1/f spectra of spatial variability in rocky intertidal assemblages
Authors: Tamburello Laura , Bulleri Fabio , Bertocci Iacopo , Maggi Elena , Benedetti-Cecchi Lisandro
Published: May 2013

Ecological tests of 1/f‐noise models have advanced our understanding of how environmental fluctuations affect population abundance and species distributions. Most empirical studies have been conducted under controlled laboratory conditions and have focused on individual drivers. We present the results of a four‐year field experiment in which canopy presence/absence and the availability of primary space were manipulated as red‐noise and white‐noise spatial processes, respectively, to evaluate their separate and compounded effects on algal turf distribution in a rocky intertidal community. Algal turfs closely tracked spatial variation in canopy distribution, displaying a reddened spectrum of spatial variation. Surprisingly, white‐noise clearings also induced a red‐shift in turf distribution, a pattern that was related to a nonlinear relation between gap size and turf colonization. The two disturbances interacted antagonistically, dampening the red‐shift of turf distribution. Our results provide evidence of experimentally induced shifts in the spectrum of a spatial variable under natural environmental conditions.
Cytotype differences modulate eco‐geographical differentiation in the widespread plant Centaurea stoebe
Authors: Hahn Min A. , Müller-Schärer Heinz
Published: May 2013

The evolution of optimal life history strategies is central for the fitness of organisms in a given environment. Besides divergent selection, other factors may determine regional patterns of differentiation and contribute to life history evolution. In a common‐garden environment over three years, we examined life history differentiation across different eco‐geographical regions and effects of a specialist root‐insect herbivore in the widespread European plant Centaurea stoebe, spotted knapweed. This plant occurs as two cytotypes with contrasting life cycles: monocarpic diploids and polycarpic tetraploids. In addition, the tetraploid cytotype has more recently become invasive in North America. We found significant regional differentiation in traits related to the timing of reproduction and reproductive allocation, but contrasting patterns in diploids and tetraploids. In diploids the degree of regional differentiation was higher compared to native tetraploids, and in the latter compared to invasive tetraploids. Furthermore, a pronounced shift in environmental conditions between the native and introduced range could have contributed to the differentiation between native and invasive tetraploids. The study also revealed the potential of the root‐mining insect herbivore Agapeta zoegana, used as a biological control organism, to increase plant performance (presumably through overcompensatory growth), especially in the polycarpic tetraploids, and more so in the introduced populations. These findings suggest that patterns of regional differentiation in C. stoebe may be partly determined by divergent selection, but also strongly modulated by life cycle differences among geo‐cytotypes. Furthermore, our study highlights the importance in applying a comprehensive and long‐term approach when studying regional differentiation in plants.
Do invasive species perform better in their new ranges?
Authors: Parker John D. , Torchin Mark E. , Hufbauer Ruth A. , Lemoine Nathan P. , Alba Christina , Blumenthal Dana M. , Bossdorf Oliver , Byers James E. , Dunn Alison M. , Heckman Robert W. , Hejda Martin , Jarošík Vojtěch , Kanarek Andrew R. , Martin Lynn B. , Perkins Sarah E. , Pyšek Petr , Schierenbeck Kristina , Schlöder Carmen , van Klinken Rieks , Vaughn Kurt J. , Williams Wyatt , Wolfe Lorne M.
Published: May 2013

A fundamental assumption in invasion biology is that most invasive species exhibit enhanced performance in their introduced range relative to their home ranges. This idea has given rise to numerous hypotheses explaining “invasion success” by virtue of altered ecological and evolutionary pressures. There are surprisingly few data, however, testing the underlying assumption that the performance of introduced populations, including organism size, reproductive output, and abundance, is enhanced in their introduced compared to their native range. Here, we combined data from published studies to test this hypothesis for 26 plant and 27 animal species that are considered to be invasive. On average, individuals of these 53 species were indeed larger, more fecund, and more abundant in their introduced ranges. The overall mean, however, belied significant variability among species, as roughly half of the investigated species (N = 27) performed similarly when compared to conspecific populations in their native range. Thus, although some invasive species are performing better in their new ranges, the pattern is not universal, and just as many are performing largely the same across ranges.
Capturing the Effect of Fracture Heterogeneity on Multiphase Flow During Fluid Injection
Authors: Jonoud S.. , Wennberg O.P.. P. , Casini G.. , Larsen J.A.. A.
Published: May 2013

Carbonate fractured reservoirs introduce a tremendous challenge to the upscaling of both single- and multiphase flow. The complexity comes from both heterogeneous matrix and fracture systems in which the separation of scales is very difficult. The mathematical upscaling techniques, derived from representative elementary volume (REV), must therefore be replaced by a more realistic geology-based approach. In the case of multiphase flow, an evaluation of the main forces acting during oil recovery must also be performed.

A matrix-sector model from a highly heterogeneous carbonate reservoir is linked to different fracture realizations in dual-continuum simulations. An integrated iterative workflow between the geology-based static modeling and the dynamic simulations is used to investigate the effect of fracture heterogeneity on multiphase fluid flow. Heterogeneities at various scales (i.e., diffuse fractures and subseismic faults) are considered. The diffuse-fracture model is built on the basis of facies and porosity from the matrix model together with core data, image-log data, and data from outcrop-analogs. Because of poor seismic data, the subseismic-fault model is mainly conceptual and is based on the analysis of outcrop-analog data. Fluid-flow simulations are run for both single-phase and multiphase flow and gas and water injections.

A better understanding of fractured-reservoirs behavior is achieved by incorporating realistic fracture heterogeneity into the geological model and analyzing the dynamic impact of fractures at various scales. In the case of diffuse fractures, the heterogeneity effect can be captured in the upscaled model. The subseismic faults, however, must be explicitly represented, unless the sigma (shape) factor is included in the upscaling process. A local grid-refinement approach is applied to demonstrate explicit fractures in large-scale simulation grids. This study provides guidelines on how to effectively scale up a heterogeneous fracture model and still capture the heterogeneous flow behavior.