bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostaglandin E2 receptor EP4 as the common target on cancer cells and macrophages to abolish angiogenesis, lymphangiogenesis, metastasis, and stem‐like cell functions
Authors: Majumder Mousumi , Xin Xiping , Liu Ling , Girish Gannareddy V. , Lala Peeyush K.
Published: July 2014

We previously established that COX‐2 overexpression promotes breast cancer progression and metastasis. As long‐term use of COX‐2 inhibitors (COX‐2i) can promote thrombo‐embolic events, we tested an alternative target, prostaglandin E2 receptor EP4 subtype (EP4), downstream of COX‐2. Here we used the highly metastatic syngeneic murine C3L5 breast cancer model to test the role of EP4‐expressing macrophages in vascular endothelial growth factor (VEGF)‐C/D production, angiogenesis, and lymphangiogenesis in situ, the role of EP4 in stem‐like cell (SLC) functions of tumor cells, and therapeutic effects of an EP4 antagonist RQ‐15986 (EP4A). C3L5 cells expressed all EP receptors, produced VEGF‐C/D, and showed high clonogenic tumorsphere forming ability in vitro, functions inhibited with COX‐2i or EP4A. Treating murine macrophage RAW 264.7 cell line with COX‐2i celecoxib and EP4A significantly reduced VEGF‐A/C/D production in vitro, measured with quantitative PCR and Western blots. Orthotopic implants of C3L5 cells in C3H/HeJ mice showed rapid tumor growth, angiogenesis, lymphangiogenesis (CD31/LYVE‐1 and CD31/PROX1 immunostaining), and metastasis to lymph nodes and lungs. Tumors revealed high incidence of EP4‐expressing, VEGF‐C/D producing macrophages identified with dual immunostaining of F4/80 and EP4 or VEGF‐C/D. Celecoxib or EP4A therapy at non‐toxic doses abrogated tumor growth, lymphangiogenesis, and metastasis to lymph nodes and lungs. Residual tumors in treated mice revealed markedly reduced VEGF‐A/C/D and phosphorylated Akt/ERK proteins, VEGF‐C/D positive macrophage infiltration, and proliferative/apoptotic cell ratios. Knocking down COX‐2 or EP4 in C3L5 cells or treating cells in vitro with celecoxib or EP4A and treating tumor‐bearing mice in vivo with the same drug reduced SLC properties of tumor cells including preferential co‐expression of COX‐2 and SLC markers ALDH1A, CD44, OCT‐3/4, β‐catenin, and SOX‐2. Thus, EP4 is an excellent therapeutic target to block stem‐like properties, angiogenesis, and lymphangiogenesis induced by VEGF‐A/C/D secreted by cancer cells and tumor infiltrating macrophages.
Proteome changes induced by laser in diabetic retinopathy
Authors: Quin Godfrey J , Lyons Brian , Len Alice CL , Madigan Michele C , Gillies Mark C
Published: July 2014

Background

Diabetic macular oedema (DMO) is the commonest cause of vision loss in people with diabetes. Laser photocoagulation can be effective in the treatment ofDMO; however, its mechanism of action is still poorly understood. A better understanding of these mechanisms may allow the development of therapeutic approaches that could avoid the deleterious adverse events associated with photocoagulation.

Methods

We have used proteomic techniques to identify the protein changes induced by threshold intensity retinal laser treatment in a rodent model of diabetic retinopathy. Retinae were obtained from diabeticDarkAgouti rats 8 weeks following laser treatment. Extracted proteins from lasered and non‐lasered diabetic retinae were separated and compared using two‐dimensional gel electrophoresis.

Results

Image analysis revealed 24 protein spots with decreased expression after laser treatment and 9 spots with increased expression. On lasered retinal gels, four spots were uniquely expressed, with eight unique spots on non‐lasered gels. Twenty‐two protein spots of interest were identified using matrix‐assisted desorption ionization‐mass spectrometry with database matching. Following laser,Wnt‐5 beta,LEK‐1,GADPH, claudin‐12 and calretinin were significantly down‐regulated in expression.

Conclusions

The present study provides a proteomic insight into the underlying biological basis for the therapeutic effects of laser forDMO. We provide further evidence of the involvement ofWnt pathway signalling in the neural retina inDMO, and for up to 2 months following laser treatment. Changes inLEK‐1 and claudin‐12 may have effector roles, and changes in glyceraldehyde‐3‐phosphate dehydrogenase and calretinin may reflect the altered retinal microenvironment resulting from laser treatment.
Quantum biology of the retina
Authors: Sia Paul Ikgan , Luiten André N , Stace Thomas M , Wood John PM , Casson Robert J
Published: July 2014

The emerging field of quantum biology has led to a greater understanding of biological processes at the microscopic level. There is recent evidence to suggest that non‐trivial quantum features such as entanglement, tunnelling and coherence have evolved in living systems. These quantum features are particularly evident in supersensitive light‐harvesting systems such as in photosynthesis and photoreceptors. A biomimetic strategy utilizing biological quantum phenomena might allow new advances in the field of quantum engineering, particularly in quantum information systems. In addition, a better understanding of quantum biological features may lead to novel medical diagnostic and therapeutic developments. In the present review, we discuss the role of quantum physics in biological systems with an emphasis on the retina.
‘Weekend on the town’: Discrete sessions of drug use for a sample of young psychostimulant users
Authors: Jenkinson Rebecca , Jolley Damien , Dietze Paul
Published: July 2014

Introduction and Aims

Few epidemiological studies have examined the behaviours and experiences of young adults during discrete drug‐use events. This study was designed to capture a rich, detailed description of discrete occasions or ‘sessions’ of psychostimulant use.

Design and Methods

Participants were 220 young psychostimulant users living in Melbourne, Australia, recruited through targeted advertising in entertainment street press, on websites, at events/dance parties and through peer referral between September 2007 and March 2008. The research identified the timing, sequence, frequencies, quantities and modes of alcohol and other drug administration during the participants' most recent session of psychostimulant use and explored the contexts and settings in which drug use took place.

Results

Participants were well‐educated young people who used a variety of different drugs. Their most recent session of psychostimulant use was reported as highly enjoyable and typical of their other sessions of psychostimulant use. The session lasted a median of 20 h, and in most cases, simultaneous drug use was the norm, and large quantities of alcohol, psychostimulants and other drugs were consumed. Acquisition of illicit drugs commonly occurred through social networks during the course of the session and significant sums of money were reportedly spent.

Discussion and Conclusions

Findings point to a range of priorities for future research and public health interventions aimed at young psychostimulant users, focused primarily on reducing the prevalence and consequences of simultaneous and heavy/binge drug use. [Jenkinson R, Jolley D, Dietze P. ‘Weekend on the town’: Discrete sessions of drug use for a sample of young psychostimulant users. Drug Alcohol Rev 2014; 33:428‐435]
DRG‐Benchmarking: Analyse von Leistungsstrukturen und ‐unterschieden in dermatologischen Kliniken
Authors: Fürstenberg Torsten , Gierling Patrick , Irps Sebastian , Gollnick Harald , Kaufmann Roland , Stadler Rudolf , Rompel Rainer , Hensen Peter
Published: July 2014

Hintergrund

Im Kontext der DRG‐basierten Krankenhausfinanzierung ist die Analyse des Leistungsspektrums der stationären Dermatologie von dauerhaft hohem Interesse. Im Rahmen eines Benchmarking‐Projekts sollten Leistungsstrukturen und ‐unterschiede anhand von Kennzahlen vergleichend untersucht werden.

Methodik

Für die multizentrische Querschnittsstudie wurden Routinedaten von 46 deutschen dermatologischen Kliniken und Abteilungen erhoben, bearbeitet und analysiert. Für die Auswertung standen 95 257 Datensätze aus dem Jahr 2011 zur Verfügung, die nach der Systematik des G‐DRG‐Systems Version 2013 gruppiert wurden.

Ergebnisse

Die durchschnittliche Verweildauer aller Fälle liegt bei 6,3 Tagen (Normallieger: 5,7 Tage) bei einem durchschnittlichen Patientenalter von 52 Jahren. Insgesamt werden 55 % aller Fälle medizinischen, 45 % operativen DRGs zugeordnet. Einundsiebzig Prozent der Einrichtungen liegen innerhalb dieses Mittelwertes (± 10 %). Es konnte für die Stichprobe kein Zusammenhang zwischen der Bettenzahl der Einrichtung und dem angebotenen Leistungsspektrum nachgewiesen werden. Große Unterschiede zwischen den Einrichtungen zeigten Kennzahlen der Kodierqualität.

Schlussfolgerungen

Die Ergebnisse spiegeln die heterogene Behandlungswirklichkeit der stationären Dermatologie in Deutschland wider. Die Unterschiede in der Leistungserstellung machen deutlich, dass sie neben patientenbezogenen Einflussfaktoren insbesondere auch von den infrastrukturellen Bedingungen und den verfügbaren Ressourcen an den jeweiligen Standorten geprägt sind.
Cost of diabetic foot disease to the National Health Service in England
Authors: Kerr M. , Rayman G. , Jeffcoate W. J.
Published: July 2014

Aim

To estimate the annual cost of diabetic foot care in a universal healthcare system.

Methods

National datasets and economic modelling were used to estimate the cost of diabetic foot disease to the National Health Service in England in 2010–2011. The cost of hospital admissions specific to foot disease or amputation was estimated from Hospital Episode Statistics and national tariffs. Multivariate regression analysis was used to estimate the impact of foot disease on length of stay in admissions that were not specific to foot disease or amputation. Costs in other areas were estimated from published studies and data from individual hospitals.

Results

The cost of diabetic foot care in 2010–2011 is estimated at £580m, almost 0.6% of National Health Service expenditure in England. We estimate that more than half this sum (£307m) was spent on care for ulceration in primary and community settings. Of hospital admissions with recorded diabetes, 8.8% included ulcer care or amputation. Regression analysis suggests that foot disease was associated with a 2.51‐fold (95% CI 2.43–2.59) increase in length of stay.The cost of inpatient ulcer care is estimated at £219 m, and that of amputation care at £55 m.

Conclusions

The cost of diabetic foot disease is substantial. Ignorance of the cost of current care may hinder commissioning of effective services for prevention and management in both community and secondary care.
Interactions between pollinator and non‐pollinator fig wasps: correlations between their numbers can be misleading
Authors: Raja Shazia , Suleman Nazia , Quinnell Rupert J. , Compton Stephen G.
Published: July 2014

Ficusand their species–specific pollinator fig wasps represent an obligate plant–insect mutualism, but figs also support a community of non‐pollinating fig wasps (NPFWs) that consist of phytophages and parasitoids or inquilines. We studied interactions betweenKradibia tentacularis, the pollinator of a dioecious fig tree speciesFicus montana, and an undescribedNPFW Sycoscaptersp. Members ofSycoscaptersp. oviposited 2–4 weeks after pollinator oviposition, when host larvae were present in the figs. No negative correlation was found between the numbers of the two wasp species emerging from figs in a semi‐natural population. However, in experiments where the numbers of pollinator foundresses entering a fig were controlled,Sycoscaptersp. significantly reduced the numbers of pollinator offspring. Consequently, it can be concluded thatSycoscaptersp. is a parasitoid ofK. tentacularis(which may also feed on plant tissue).Sycoscapterfemales concentrate their oviposition in figs that contain more potential hosts, rendering invalid conclusions based on simple correlations of host and natural enemy numbers.
Development in the Usage and Comprehension of Greeting Calls in a Free‐Ranging Group of Japanese Macaques (Macaca fuscata)
Authors: Katsu Noriko , Yamada Kazunori , Nakamichi Masayuki
Published: July 2014

The main objective of this study is to clarify the developmental process involved in both the usage of greeting calls and the response to greeting calls by Japanese macaques. These greeting calls facilitate affiliative interactions by communicating benign intent. Specifically, individuals frequently emit greeting calls when interacting with less‐predictable individuals. Here, we examined whether the targets at which greeting calls are directed, along with associated behavioral responses, differed among the age classes, by conducting a cross‐sectional observation of females aged 0–5 yr and their mothers. We found that infant females showed a weak tendency to emit greeting calls at no specific receivers, unlike that by older females. Adult females emitted greeting calls more frequently when approaching unrelated females than related females. In contrast, young adult or juvenile females exhibited no significant difference in the proportion of the calls with related and unrelated conspecifics. Adult and young adult females were more likely to respond affiliatively to other individuals that approached using greeting calls compared with silent approaches, whereas juveniles did not exhibit different responses to the two types of approaches. This study showed that the target‐specific usage and affiliative response to greeting calls emerge with changes in the developmental stage. Furthermore, the fact that even young adults did not use greeting calls as adults indicates that the usage of greeting calls is modified in conjunction with the expansion of social relationships.
Pulmonary pharmacokinetics of desfuroylceftiofur acetamide after nebulisation or intramuscular administration of ceftiofur sodium to weanling foals
Authors: Fultz L. , Giguère S. , Berghaus L. J. , Grover G. S. , Merritt D. A.
Published: July 2014

Reasons for performing study

Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data.

Objectives

To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation.

Study design

Randomised experimental study.

Methods

Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. route and 6 foals received the same dose by nebulisation. Concentrations ofDCAin plasma andPELFwere measured after Doses 1 and 5, and differential cell counts were performed on bronchoalveolar lavage samples obtained after Dose 5.

Results

Foals receiving ceftiofur sodium via nebulisation had significantly lower peak concentrations (0.15 ± 0.12 vs. 6.15 ± 0.75 mg/l) and area under the curve (1.26 ± 0.96 vs. 37.63 ± 4.01 mg●h/l) in plasma compared with those receiving the drug by the i.m. route. In contrast, foals receiving ceftiofur sodium via nebulisation had significantly higher peak concentrations (4.52 ± 2.91 vs. 0.73 ± 0.73 mg/l) and area under the curve (24.14 ± 14.09 vs. 5.91 ± 3.28 mg●h/l) inPELFcompared with those receiving the drug by the i.m. route. Cell concentration and differential cell count in bronchoalveolar lavage fluid of foals nebulised with ceftiofur sodium were not significantly different from those of foals nebulised with saline.

Conclusions

Administration of ceftiofur sodium via nebulisation is well tolerated andDCAconcentrations inPELFremain above the minimum inhibitory concentration of the drug required to inhibit the growth of 90% ofStreptococcus zooepidemicusfor approximately 24 h after administration. Nebulised ceftiofur sodium warrants further investigation for the treatment of bacterial infections of the lower respiratory tract in horses.
Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals
Authors: Knych H. K. , Steffey E. P. , Casbeer H. C. , Mitchell M. M.
Published: July 2014

Reasons for performing study

Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use.

Objectives

To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5–13 days and describe selected, associated dose‐ and time‐related behavioural and physiological responses to plasma fentanyl concentration.

Study design

Experimental.

Methods

Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10‐min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes.

Results

Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half‐life following administration of the final dose was 44.2 ± 9.85 min.

Conclusions

Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow.
NADPH oxidase‐2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis
Authors: Zhang Guo‐You , Wu Liang‐Cai , Dai Tao , Chen Shi‐Yi , Wang An‐Yuan , Lin Kang , Lin Da‐Mu , Yang Jing‐Quan , Cheng Biao , Zhang Li , Gao Wei‐Yang , Li Zhi‐Jie
Published: July 2014

The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor‐beta1 (TGF‐β1) exerts pro‐oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF‐β1‐induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real‐time Q‐PCR and Western blotting analyses were used for mRNA and protein detection. In addition, siRNA technology was applied for gene knock‐down analysis. Hydrogen peroxide production and 2′,7′‐dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non‐phagocytic NADPH oxidase mRNA. TGF‐β1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF‐β1 phosphorylated MAPKs and increased activator protein‐1 (AP‐1) in a redox‐sensitive manner, and NOX2 suppression inhibited baseline and TGF‐β1‐mediated stimulation of Smad2 phosphorylation. Moreover, TGF‐β1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and bFGF and PAI‐1 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.
Topical hesperidin prevents glucocorticoid‐induced abnormalities in epidermal barrier function in murine skin
Authors: Man George , Mauro Theodora M. , Kim Peggy L. , Hupe Melanie , Zhai Yongjiao , Sun Richard , Crumrine Debbie , Cheung Carolyn , Nuno‐Gonzalez Almudena , Elias Peter M. , Man Mao‐Qiang
Published: July 2014

Systemic and topical glucocorticoids (GC) can cause significant adverse effects not only on the dermis, but also on epidermal structure and function. In epidermis, a striking GC‐induced alteration in permeability barrier function occurs that can be attributed to an inhibition of epidermal mitogenesis, differentiation and lipid production. As prior studies in normal hairless mice demonstrated that topical applications of a flavonoid ingredient found in citrus, hesperidin, improve epidermal barrier function by stimulating epidermal proliferation and differentiation, we assessed here whether its topical applications could prevent GC‐induced changes in epidermal function in murine skin and the basis for such effects. When hairless mice were co‐treated topically with GC and 2% hesperidin twice‐daily for 9 days, hesperidin co‐applications prevented the expected GC‐induced impairments of epidermal permeability barrier homoeostasis and stratum corneum (SC) acidification. These preventive effects could be attributed to a significant increase in filaggrin expression, enhanced epidermal β‐glucocerebrosidase activity and accelerated lamellar bilayer maturation, the last two likely attributable to a hesperidin‐induced reduction in stratum corneum pH. Furthermore, co‐applications of hesperidin with GC largely prevented the expected GC‐induced inhibition of epidermal proliferation. Finally, topical hesperidin increased epidermal glutathione reductase mRNA expression, which could counteract multiple functional negative effects of GC on epidermis. Together, these results show that topical hesperidin prevents GC‐induced epidermal side effects by divergent mechanisms.
Post‐translational modification and extended glycosylation pattern of a plant latex peroxidase of native source characterized by X‐ray crystallography
Authors: Palm Gottfried J. , Sharma Anurag , Kumari Moni , Panjikar Santosh , Albrecht Dirk , Jagannadham Medicherla V. , Hinrichs Winfried
Published: July 2014

The crystal structure of banyan peroxidase purified from the latex of Ficus benghalensis has been solved at 1.67 Å resolution by single‐wavelength anomalous diffraction phasing. The refined structure includes 306 amino acid residues, a heme and two calcium ions. The protein belongs to class III peroxidases and is the first one from plant latex. Extensive glycosylation was observed with N‐linked glycans attached to seven asparagine residues. The enzyme is stable with respect to a wide pH range, temperature, chemical denaturants and organic solvents, probably as a result of its high glycosylation. An unexpected post‐translational modification of Asp290 was identified as succinimide moiety. Kinetic parameters of banyan peroxidase have been determined using various hydrogen donor substrates and hydrogen peroxide.

Database

Coordinates and structure factors have been deposited in the Protein Data Bank under accession number 4CUO.
An inter and intra‐regional exploration of the marine sector employment and deprivation in England
Authors: Morrissey Karyn
Published: July 2014

There is an assumption that marine activities, particularly seafood‐based activities, are an important source of employment and income in poor coastal areas. Linking the 2010 Index of Multiple Deprivation (IMD) for England with the 2010 Business Structure Dataset (BSD), this paper examines whether employment in the marine sector is concentrated in areas of high deprivation as is assumed. Merging the IMD 2010 with the BSD allows us to examine rates of marine‐based employment and their location both across (inter) and within (intra) regions. This analysis provides the first empirical evidence that employment in the marine sector, particularly fishing and seafood processing, are located in areas with higher than average deprivation, even if the overall regional rate of deprivation is relatively low (the South East and the South West of England). Methodologically, this analysis indicates that an index such as the IMD based on a wide range of social and economic data can be used to understand the socioeconomic impacts of a sector within an area. Whilst most importantly this paper further demonstrates that intra‐regional analysis is more insightful in exploring the geographical socioeconomic impact of the marine sector than inter‐regional level analysis. With regard to the academic contribution, this paper also aims to conceptualise marine activity as a core economic activity located both in peripheral and non‐peripheral areas.
Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case
Authors: Hokuto Daisuke , Yamato Ichiro , Nomi Takeo , Yasuda Satoshi , Obara Shinsaku , Yamada Takatsugu , Chihiro Kawaguchi , Nakajima Yoshiyuki
Published: July 2014

Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.
Influence of lifestyle‐related diseases and age on the development and progression of non‐alcoholic fatty liver disease
Authors: Shima Toshihide , Seki Kojiro , Umemura Atsushi , Ogawa Rie , Horimoto Ryuji , Oya Hirohisa , Sendo Rei , Mizuno Masayuki , Okanoue Takeshi
Published: July 2014

Aim

Although non‐alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, the clinical association between non‐alcoholic steatohepatitis (NASH) and lifestyle‐related diseases such as obesity, type 2 diabetes mellitus (DM), hypertension (HT) and dyslipidemia (DL) has not been clarified. We studied the influence of lifestyle‐related diseases and age on the development and progression of NAFLD.

Methods

We enrolled 550 patients with biopsy‐proven NAFLD (284 men, 266 women; average age, 52 and 62 years, respectively). The effect of lifestyle‐related diseases and age (≤49 vs ≥50 years) on the frequency of NASH and advanced fibrosis (≥stage 3) was studied.

Results

Prevalence of obesity, DM, HT and DL in male and female NASH patients was 75%/67%, 53%/54%, 66%/77% and 85/79%, respectively. DM patients had a higher frequency of NASH in the older male NAFLD group and a higher frequency of advanced fibrosis in the older female NASH group. With the increasing number of complicating lifestyle‐related diseases, the rate of NASH increased in male NAFLD patients. In both sexes, aging resulted in the development of NASH and progression of liver fibrosis. Multivariate logistic regression analysis revealed that age and DM were significantly associated with the development of NASH in male NAFLD patients and progression of fibrosis in female NASH patients.

Conclusion

Age is strongly associated with the development and progression of NASH. Type 2 DM may play the most crucial role among lifestyle‐related diseases in the development and progression of NASH.
Type 1 lepra reaction in histoid leprosy
Authors: Singh Nidhi , Kumari Rashmi , Gupta Divya , Thappa Devinder Mohan , Ganesh Rajesh Nachiappa
Published: July 2014

Objectives

Lepra reaction in histoid leprosy (HL) is rare; there are few reports of type 2 lepra reaction in HL. We report a 42‐year‐old woman with HL in type 1 lepra reaction after 10 weeks of multibacillary multi‐drug therapy (MBMDT).

Case report

A 42‐year‐old woman presented with asymptomatic multiple papules, plaques, and nodules over the face, trunk, and extremities and no history of prior treatment with anti‐leprosy drugs. A biopsy of a skin nodule on the forearm revealed spindle‐shaped, non‐vacuolated histiocytes in a whorled pattern with abundant acid‐fast bacilli (AFB). The patient was diagnosed with HL and started on MBMDT. Ten weeks later, she developed pruritic, painful, erythematous, and edematous papules, plaques, and nodules over the face, trunk, and extremities, without constitutional symptoms. Histopathology revealed an atrophic epidermis, preserved grenz zone, and papillary dermal edema. Elongated AFB were visible on Fite's stain. The MBMDT was continued, along with nonsteroidal anti‐inflammatory drugs and antihistamines, but pruritus, pain, erythema, and edema persisted, and new skin lesions appeared. The patient was started on prednisolone at 0.75 mg/kg body weight/day. Prednisolone resulted in symptomatic relief and the healing of ulcerated papules within four weeks. Treatment was tapered and stopped after 20 weeks.

Conclusions

Histoid leprosy is considered a variant of lepromatous leprosy, which rarely involves a lepra reaction. Pruritus and ulceration of skin lesions as manifestations of type 1 lepra reaction in HL have not been reported previously. These symptoms manifested after 10 weeks of MBMDT and responded well to oral prednisolone.
Inhibition by Phenoxybenzamine of the Noradrenaline Releasing Effect of Tyramine
Authors: Hedqvist P. , Oliverio A. , Stjärne L.
Published: July 2014

Hedqvist, P., A. Oliverio and L. Stjärne, Inhibition by phenoxybenzamine of the noradrenaline releasing effect of tyramine. Acta physiol. scand. 1968. 72. 385–391.

After loading the isolated, perfused dog spleen with tritium‐labeled noradrenaline intra‐arterial injections of tyramine were found to cause an increase in the overflow of both labeled, exogenous, and of endogenous noradrenaline into the effluent from the organ. The overflow response to 2–3 consecutive injections of a standard dose of tyramine remained relatively constant. Increasing the tyramine dose up to 100‐fold resulted in a marked increase in the pressor response but did not produce a proportional increase in the overflow of noradrenaline. Phenoxybenzamine added to the perfusion fluid strongly reduced or completely abolished the overflow response to tyramine.
Extravascular Shunting of Oxygen in the Small Intestine of the Cat
Authors: Kampp Mogens , Lundgren Ove , Nilsson Nils Johan
Published: July 2014

Kampp, M., O. Lundgren and N. J. Nilsson. Extravascular shunting of oxygen in the small intestine of the cat. Acta physiol. scand. 1968. 72. 396–403.

At “resting” intestinal blood flow the venous appearance time of intra‐arterially injected red cells labelled with methemoglobin exceeded by 1–2 sec that of oxygen administered in an identical manner. This observation is taken to indicate an extravascular shunting (countercurrent exchange) of oxygen between the ascending and descending limbs of the mucosal vascular loops located mainly in the villi. During vasodilatation induced by isopropylnoradrenaline or vasoconstriction induced by stimulation of the regional sympathetic fibres (4 imp/sec) no difference in venous appearance time between red cells and oxygen could be demonstrated. The physiological significance of the findings of the present study is discussed.
Posthypertonic Hemolysis in Sodium Chloride Systems
Authors: Zade‐Oppen A. M. M.
Published: July 2014

Human erythrocytes were exposed in vitro to hypertonic NaCl solutions and then to near isotonic media. The resulting posthypertonic hemolysis was studied as a function of hypertonic concentration and of time in the hypertonic medium. Providing that a critical concentration level (∼1.5 M NaCl) is exceeded, posthypertonic hemolysis is proportional both to the duration of exposure to hypertonicity and to the hypertonic concentration. The results have been interpreted in terms of a hypothesis put forward by Söderström (1944), who postulated that influx of salt occurred during the hypertonic phase and that a later reduction of the external concentration caused osmotic hemolysis. A rough calculation suggests that only above an external concentration of 0.65 M NaCl will an influx of salt occur. An analysis of the results in terms of this hypothesis suggested that the permeability of the cells to NaCl increases with increasing external NaCl concentration: The permeability increase was very great in the region of 3 M NaCl. The counter‐current multiplier mechanism for kidney function has been criticised on the ground that red cells may not tolerate the tonicity changes postulated to exist in the kidney. In vitro experiments using slightly worse conditions than are believed to exist in the human kidney showed no significant hemolysis.
The Metabolism of Human Spermatozoa in the Presence of Prostaglandin E1
Authors: Eliasson R. , Murdoch R. N. , White I. G.
Published: July 2014

The oxygen uptake and metabolism of human spermatozoa has been measured using concentrated suspensions of cells incubated with radioactive fructose in small Warburg flasks. The oxygen uptake was about 14 μl per 10S sperm per hr and represented true respiratory activity since radioactive carbon dioxide was produced as well as lactic acid.

The presence of 100 μg of prostaglandin E1 per ml had no effect on oxygen uptake, the amount of fructose metabolised or the amount of lactic acid accumulating.
Oxygen Uptake during Pinocytosis in Amoeba Proteus
Authors: Hansson S. E. , Johansson G. , Josefsson J.‐O.
Published: July 2014

The oxygen uptake of Amoeba proteus was measured by the Cartesian ampulla diver technique. The intensity of pinocytosis was determined by counting the number of channels developed during the first 20 min of the pinocytosis induced by potassium chloride. Addition of calcium ions was used to inhibit pinocytosis induced by Tris. The oxygen uptake of the amoeba in culture medium was found to be 2.5 ± 0.9 μl/hr/cell at 25° C. Transient increases in rate of oxygen uptake were observed with different salt solutions. The intensity of respiratory stimulation varied in proportion to the activity of the salt as a pinocytosis inducer. Inhibition of Tris‐induced pinocytosis by calcium and potentiation of potassium‐pinocytosis by lanthanum decreased and respectively increased the respiratory rate of the amoeba. The time course of the development of channels was similar to that of th stimulated oxygen uptake. From experiments with a calcium‐binding agent (EGTA) it was concluded that respiratory stimulation secondary to the increase of the permeability of the cell‐membrane during pinocytosis might add to the energy expenditure during the formation of channels. As with the pinocytosis phenomenon calcium exhibited a dual action on the stimulated oxygen uptake: A minimal concentration was necessary for both processes while addition of calcium inhibited respiratory stimulation as well as pinocytosis.
Position and Velocity Sensitivity of Muscle Spindles in the Cat. II. Dynamic Fusimotor Single‐Fibre Activation of Primary Endings
Authors: Lennerstrand Gunnar , Thoden Uwe
Published: July 2014

Impulse frequency responses of cat primary muscle spindle endings to ‘triangular’ length changes were recorded during stimulation of single dynamic fusimotor γ‐fibres at a constant rate. Endings in the ankle extensor and flexor muscles were studied. The dynamic fusimotor effects consisted of an unchanged or decreased position sensitivity of the endings and an increased velocity sensitivity to length increment. The effects were quantitatively similar in primary endings of all the muscle studied. In the velocity response, which was subdivided into ‘quick’ and ‘slow’ components, the ‘slow’ velocity response was increased much more by the stimulation than the ‘quick’ velocity response. The velocity sensitivity to length decrement could usually not be exactly determined. In the few cases in which it could be assessed, it seemed to be lower than the velocity sensitivity to length increment. When relatively high rates of stimulation and high velocities of length change were applied to the endings, a velocity dependent ‘saturation’ of the response appeared. In the discussion interest is focused on spindle mechanisms responsible for generating the observed response. It is suggested that the response is derived from intrafusal components with the mechanical and electrical characteristics of amphibian slow muscle fibres.
Position and Velocity Sensitivity of Muscle Spindles in the Cat. III. Static Fusimotor Single‐Fibre Activation of Primary and Secondary Endings
Authors: Lennerstrand Gunnar , Thoden Uwe
Published: July 2014

During the tetanic stimulation of single static fusimotor fibres, primary and secondary endings in ankle extensor and flexor muscles of the cat have been subjected to ‘triangular’ length changes. Position and velocity sensitivities were determined and compared with those obtained in non‐activated endings. Two types of action of static fibre stimulation on the position sensitivity have been observed both in primary and secondary endings: it was either unchanged, or it decreased with increasing rate of stimulation (type I effect); it increased with increasing rate of stimulation (type II effect). The distribution of the two types was different to primary and secondary endings and to extensor and flexor endings. During stimulation of most static fibres, irrespective of their type, the velocity responses of both primary and secondary endings resembled those of non‐activated secondary endings. The ‘quick’ component of the velocity response was usually larger in primary than in secondary endings, while the ‘slow’ components were about the same. Comparisons made in secondary endings between the velocity responses during static activation and in the non‐activated state showed that the ‘quick’ component was reduced and the ‘slow’ component increased by the stimulation. ‘Exceptional’ velocity responses were observed in type I activation of some primary endings.
Afferent and Efferent Activity in the Renal Nerves of Cats
Authors: ÅStröm A. , Grafoord J.
Published: July 2014

In anesthetized cats efferent as well as afferent activity has been recorded in the kidney nerves. Pulse synchronous bursts of efferent impulses could regularly be recorded which after vagotomy and baroreceptor denervation were augmented and changed into a continuous type of discharge. The efferent activity could be modified by electrical stimulation of peripheral sensory nerves. It was inhibited by elevation of systemic blood pressure by i.v. noradrenaline injection, and greatly increased by lowering of blood pressure by i.v. acethylcholine. In the same nerves afferent activity also occurred, in a few instances spontaneously, but more often after elevation of renal vein pressure, elevation of arterial perfusion pressure (by pump), mechanical pressure applied to the hilus area or local dilution of the blood by close intraarterial injection of Ringer solution. Local ischemia for one minute or less elicited intense afferent activity. The results indicate that venous distension and increased subcapsular pressure are adequate stimuli for these afferent responses and (hat more than one kind of fibers are engaged in the afferent response. The functional significance of the afferent activity remains to be determined.
The Effect of Pulmonary Artery Occlusion on the Sulfomucopolysaccharide Synthesis and Collagen Content in Rat Lungs
Authors: Boström Harry , Božović Ljubomir , Božović Milica
Published: July 2014

In rats the left branch of the pulmonary artery was occluded. The incorporation of 35S in lungs was studied till the eleventh day after operation. The hexosamine and hydroxyproline content of the lungs was determined on the first and fourth day after occlusion. The incorporation of 35S is significantly increased on the fourth day and is maximal on the sixth day. Eleven days after operation the incorporation is significantly lower than on the sixth day. During the time studied the hexosamine and hydroxyproline content of the occluded lungs increased, but the difference was significantly changed only for hexosamine after the fourth day. The significance of the results obtained for the understanding of various pathologic changes is briefly discussed.
Effect of Noradrenaline on the Elimination of Exogenous Lipids from the Blood
Authors: Hallberg Dag
Published: July 2014

The rate of elimination from the blood stream of a fat emulsion, used for parenteral nutrition, was studied in 12 dogs before and during noradrenaline infusion at constant rate. The volume of distribution of the injected emulsion (the lipid space) was larger than and highly correlated to the plasma volume. The noradrenaline infusion reduced both the plasma volume and the lipid space in all the dogs, excluding two in which an increase was observed. The zero order rate constant (K1 mmoles/l plasma/min) for the elimination of the emulsion‐triglycerides at high concentrations varied inversely with the change in plasma volume (r = 0.93). K1 × plasma volume was not influenced by the noradrenaline infusion. The first order rate constant (K2 per min) for the elimination of emulsion‐triglycerides at low concentrations decreased during the noradrenaline infusion in all the dogs, except two which had increased plasma volume. In these two dogs K2 increased. In 3 dogs the relation between K1 and plasma volume was studied before and after a plasma transfusion. The results indicate that the product K1 × plasma volume was constant. The nature of the rate constants K1 and K2 are discussed in terms of metabolic physiology, i.e. the relation between enzymatic activities, the rate of transportation of substrate, and the variations in volume of distribution of the substrate.
Activity of Pilomotor Muscles of Single Tactile Hairs in the Cat
Authors: Nilsson Bengt Y.
Published: July 2014

Contractions of the pilomotor muscles of individual carpal tactile sinus hairs in the cat were studied by simultaneous recording of the movement of a single hair by means of a capacitance meter, and of the electrical activity during the muscle contraction, as recorded by an external metal microelectrode. Single shock stimulation of the nerve gave rise to a twitch contraction, whereas repetitive stimulation caused summation of contractions at frequencies higher than 0.2/sec and fusion at frequencies of 1/sec or more. The electrical response consisted of a slow potential and a superimposed spike. These components were both shown to be dependent on the stimulus strength and to be facilitated on repetitive stimulation. At stimulus frequencies higher than 3/sec the spike gradually declined in amplitude and was substituted by a rhythmic oscillation at the same rate as the stimulus. Even when no spike was recorded the contraction was sustained. Comparisons are made between the electrical activity elicited in the pilomotor muscles and the junction potentials and spikes recorded in other types of smooth muscle.
The Lactate/Pyruvate Ratios of Cerebrospinal Fluid of Rats and Cats Related to the Lactate/Pyruvate, the ATP/ADP, and the Phosphocreatine/Creatine Ratios of Brain Tissue
Authors: Granholm Lars , Kaasik Ain E. , Nilsson Lorentz , Siesjö Bo K.
Published: July 2014

The CSF and brain tissue concentrations of lactate and pyruvate were measured in cats and rats, and related to the corresponding tissue concentrations of ATP, ADP, phosphocreatine and creatine. A comparison between superficial and deep phenobarbital anaesthesia, and nitrous oxide anaesthesia, showed that the type of anaesthesia had a marked effect on the tissue metabolites with a differential influence on the lactate/pyruvate, and on the ATP/ADP and the phosphocreatine/creatine ratios. Optimal conditions for freezing and extracting the tissue were sought and were found to include freezing of the head in such a way that the ventilation and the circulation of the animals were upheld during the freezing, as well as extraction of the tissue at −15 to −20° C. The distribution of lactate and pyruvate between extra‐ and intracellular phases was investigated in both rats and cats. In all groups studied lactate and pyruvate were found in higher concentrations in CSF than in the tissue, suggesting a pH‐dependent distribution of the weak acids. In the cat, the CSF pyruvate occurred in a relatively higher concentration than lactate, indicating a specific transport mechanism for pyruvic acid.
Potentiation by Smooth Muscle Stimulants of the Hypogastric Nerve — Vas Deferens Preparation from Normal and Castrated Guinea‐Pigs
Authors: Sjöstrand Nils O. , Swedin Göran
Published: July 2014

It is shown that a variety of smooth muscle stimulants cause marked potentiation of the motor response of the isolated vas deferens to hypogastric nerve stimulation. The substances used were: adrenaline, noradrenaline, acetylcholine, histamine, serotonin, angiotensin, bradykinin, Substance P and barium chloride. The doses producing this potentiation were in most cases 10–1000 times lower than those necessary to cause a direct contraction of the vas deferens. There were no clearcut differences between castrated and normal animals. Oxytocin and vasopressin were without effect while different prostaglandins (PGE1, PGF1 and a crude PG preparation) caused inconsistent responses.

Possible mechanisms for the potentiation are discussed and it is suggested that the most probable explanation is a direct effect on the smooth muscle, but an effect on the transmitter stores of the postganglionic adrenergic neuron cannot be ruled out. Possible functional implications are further discussed.