text:
Results 201 - 250 of 945 | ||
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Heinzel A - - 2011
We aimed to investigate the subjective well-being in patients with differentiated thyroid cancer after hormone withdrawal. Since this might be confounded by psycho-oncological processes unrelated to hypothyroidism we intended to minimize such factors by only including patients with a history of uneventful follow-up examinations for several years.We investigated 67 patients ...
Shin Yu-Kyong - - 2012
Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals ...
Mooradian Arshag D - - 2011
Aging is associated with a host of alterations in thyroid gland structure and function. Some of these changes have favorable effects on longevity, whereas others are maladaptive and contribute to a decline in health and quality of life. An area of particular controversy is the diagnosis and management of subclinical ...
Veldhuis Johannes D JD Endocrine Research Unit, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. - - 2012
Direct sampling of the human spermatic veins has disclosed concomitant LH and testosterone (T) pulses, suggesting pulsatile LH concentration-dependent stimulation of T secretion. However, studies to date have examined this hypothesis using only pharmacological stimulation with hCG. The present study tests the hypothesis that age is marked by decreased T ...
Li Chenyan - - 2011
The aims of this study performed in 2007 were to verify the selection criteria proposed by the National Academy of Clinical Biochemistry (NACB) guidelines, to investigate factors that influence thyrotropin (TSH) levels, and to determine serum TSH reference range in iodine sufficient areas of China. After excluding 291 subjects, a ...
Miyashita Norikazu - - 2011
Dolly, the first mammal cloned from a somatic cell, had shorter telomeres than age-matched controls and died at an early age because of disease. To investigate longevity and lifetime performance in cloned animals, we produced cloned cows with short telomeres using oviductal epithelial cells as donor cells. At 5 years ...
Khangura Rajbir Kaur - - 2011
Sexual dimorphism refers to the differences in size, shape, etc., between males and females. The dentition's use in sex assessment has been explored and advocated owing to its strength and resistance to peri- and post-mortem insults. The study evaluated permanent maxillary incisors and canines for sexual dimorphism and estimated the ...
Juraska Janice M - - 2011
The literature on the neuroanatomical changes that occur during normal, non-demented aging is reviewed here with an emphasis on the improved accuracy of studies that use stereological techniques. Loss of neural tissue involved in cognition occurs during aging of humans as well as the other mammals that have been examined. ...
Vishwakarma N - - 2011
Teeth are well preserved after death and they exhibit remarkable sexual dimorphism. Hence, they provide excellent materials for forensic investigations intended for identification of sex. Present study was undertaken on permanent mandibular canines of 90 male and 90 female subjects of age group 17-23 years. The mesiodistal width for right ...
Somwaru Lily L - - 2011
Despite widespread use, there are no data on initiation of thyroid hormone use in older people. We report the prevalence of thyroid hormone use and predictors of thyroid hormone initiation in a population of older men and women. Thyroid hormone medication data were collected annually from 1989 to 2006 in ...
Crosier Adrienne E - - 2011
Although the cheetah routinely lives for >12 yr in ex situ collections, females > 8 yr of age reproduce infrequently. We tested the hypothesis that reproduction is compromised in older cheetah females due to a combination of a disrupted gonadal, oocyte and uterine function/integrity. We assessed (1) ovarian response to ...
Esfandyari Hadi - - 2011
This investigation was conducted to evaluate the comparative productive performances and effect of some environmental factors on wool characteristics of Arkharmerino × Ghezel (Ar × Gh) and Arkharmerino × Moghani (Ar × Mo) crossbreed sheep. The mid-side fleece samples taken from animals during 2 years (2007-2008) were analyzed. Each sample was ...
Tajar Abdelouahid - - 2011
To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. Cross-sectional. The European Male Aging Study. Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. Interviewer-assisted questionnaires to assess physical activity, health status, and mood were ...
Baisakhiya Nitish - - 2011
Odontogenic keratocyst are known for there recurrence and local bone destruction. They have bimodal age presentation. OKC is common in lower jaw than upper jaw. They are usually asymptomatic and diagnosed during radiological investigation. We are reporting this case because of its age presentation (70 years), site of presentation (maxillary canine ...
Lin-Su Karen - - 2011
Patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency typically reach a final adult height well below their mid-parental target height. The objective of this study was to examine whether GH alone or in combination with an LHRH analog (LHRHa) improved the final adult height in patients with CAH. ...
Oliveira-Neto Luiz Alves - - 2011
Abstract Objective: To analyze cephalometric features in adults with isolated growth hormone (GH) deficiency (IGHD). Materials and Methods: Nine adult IGHD individuals (7 males and 2 females; mean age, 37.8 ± 13.8 years) underwent a cross-sectional cephalometric study, including 9 linear and 5 angular measurements. Posterior facial height/anterior facial height and ...
Bhattacharya T K - - 2011
The pituitary hormone prolactin has a wide variety of functions involving growth, behavioral, and ovarian activities in chickens. The objectives of the present study were to identify polymorphisms in the prolactin promoter and estimate their effects on growth traits in White Leghorn chickens. Among 28 haplotypes found, the h1 haplotype ...
Kirkegaard Maja - - 2011
As a model of high trophic level carnivores, sledge dogs were fed from 2 to 18 months of age with minke whale blubber containing organohalogen compounds (OHC) corresponding to 128 μg PCB/day. Controls were fed uncontaminated porcine fat. Thyroid hormone levels were assessed in 7 exposed and 7 control sister ...
Pérez Iván E - - 2011
The purpose of the present study was to describe the posteroanterior cephalometric norm values from Hispanic Americans Peruvian non adults patients between years 2009 to 2010, identify possible differences between sexes and compare our results with similar studies in the literature. Data from posteroanterior cephalograms from 318 patients (177 females ...
Fasano Giovanna - - 2011
In the past few years, cryopreservation of ovarian tissue has become an established procedure proposed in many centers around the world and transplantation has successfully resulted in full-term pregnancies and deliveries in human. This prospective study aims to evaluate the feasibility of vitrifying in vitro matured oocytes (IVM) isolated at ...
Weghofer Andrea - - 2011
AMH's reported stability during periods of hormonal change makes it a practical tool in assessing ovarian reserve. However, AMH declines with age and age-specific cut-offs remain to be established in women with proven fertility. This study aims to determine age-specific ranges of AMH in women with proven fertility. Two hundred-ten ...
Gulati Rajeev R Department of Orthodontics, Purvanchal Institute of Dental Sciences, Gorakhpur, Uttar Pradesh, - - 2011
The present study was aimed at development of the cephalometric norms for orthognathic surgery for the population of eastern Uttar Pradesh in North India. This study was conducted at a dental college. The study sample consisted of 50 males and 50 females. Each lateral cephalogram was taken in occlusion and ...
Ehrenkranz Joel - - 2011
Background: Iodine deficiency is a major public health problem throughout Africa. Although salt for human consumption is said to contain adequate amounts of iodine in Uganda, iodine intake may not be optimal. We undertook a field study to assess the adequacy of iodine nutrition in western Uganda using on-site measurement ...
Rizzo M - - 2010
Like other auto-immune diseases, Hashimoto's thyroiditis (HT) results from the interaction of genetic with environmental factors. Only few studies have evaluated the year-to-year change in frequency of HT over a wide period of time. The endocrine division of our Hospital has reported a great increase in the annual frequency of ...
Zjacić-Rotkvić Vanja - - 2010
Since the 19th century, there have been sporadic attempts to attribute the changes of aging to one or another endocrine deficit and efforts to reverse these changes by various replacement therapies. This search for a hormonal 'fountain of youth' continues today.
Boucai Laura - - 2011
The use of age- and ethnicity-specific thyrotropin (TSH) reference limits decreases misclassification of patients with thyroid dysfunction. Developing such limits requires TSH measurements in different subpopulations. We determined, in the National Health and Nutrition Examination Survey III, the TSH median, 2.5th and 97.5th centiles as a function of age, and ...
Santos Maria Teresa - - 2010
Previous studies reported alterations in salivary flow rate and biochemical parameters of saliva in cerebral palsy (CP) individuals; however, none of these considered the type of neuromotor abnormality among CP individuals, thus it remains unclear whether the different anatomical and extended regions of the brain lesions responsible for the neurological ...
Hersikorn Blair D - - 2011
The wet landscape approach to oil sands tailings reclamation in the Athabasca Oil Sands region involves creating wetlands from fluid tailings in mined-out pits. We measured time to metamorphosis, thyroid hormone status, and detoxification enzyme (EROD) induction in Wood frog (Lithobates sylvaticus) tadpoles raised on reclaimed oil sands wetlands of ...
Tokushima Isao - - 2010
The guava fruit fly, Bactrocera correcta, is widely distributed in Thailand and other surrounding Southeast Asian countries, and, like the closely related sympatric species, the oriental fruit fly, B. dorsalis, infests various fruits, including guava, peach, and mango. Males of both B. correcta and B. dorsalis are strongly attracted to, ...
Moreno-Reyes Rodrigo - - 2011
Mild iodine deficiency (MID) is endemic in Belgium. Previous surveys, which assessed iodine nutrition in Belgium, focused on children. The iodine status of adults and the influence of ethnicity or seasonality on urinary iodine concentrations (UIC) have not been investigated. Since the nutritional profile of children differs from that of ...
Veres C - - 2010
The aim of this study is to define criteria for accurate representation of the thyroid in human models used to represent external beam radiotherapy (EBRT) patients and evaluate the relationship between the volume of this organ and clinical and anthropometric characteristics. From CT images, we segmented the thyroid gland and ...
Drozdovitch Vladimir V Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, Bethesda, MD, 20892-7238, USA. - - 2011
The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the US National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to ...
Santos M - - 2010
The development of the mammary gland is a puzzling phenomenon and the research on this field has been focussed mostly on the carcinogenesis, with a less goal-oriented concern in basic histology. In order to determine the histological features of normal mammary gland in the different oestrous phases we used 39 ...
Corsonello Andrea - - 2010
several studies suggest that a decreased thyroid activity might be favourable in oldest-old subjects and that subclinical thyroid hyperfunction may be detrimental. to verify whether declining levels of circulating thyroid hormones may contribute to longevity. cross-sectional observational study. all subjects were born in Calabria (southern Italy) and their ancestry in ...
Rozing M P - - 2010
A relation between low thyroid activity and prolonged life span in humans has been observed. Several studies have demonstrated hereditary and genetic influences on thyroid function. The objective of the study was to test whether low thyroid activity associated with extreme longevity constitutes a heritable phenotype, which could contribute to ...
Filipsson Nyström H - - 2010
Sweden has had a salt iodination program since 1936. This first national surveillance study on iodine nutrition infers an adequate level of urinary iodine concentration (UIC 125 μg/l) and the aim is now to evaluate thyroid volume (Tvol) in the same national sample. A stratified probability proportionate to size cluster sampling ...
Antico-Arciuch V G VG Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, - - 2010
It is well known that thyroid disease is more frequent in women than in men; however, the molecular basis for this gender-based difference is still poorly understood. The activation of phosphoinositide 3-kinase (PI3K), through different mechanisms including loss of the PTEN tumor suppressor, is being increasingly recognized as a major ...
Aminorroaya Ashraf - - 2010
This cross-sectional study investigated the prevalence of goitre in Isfahan, a centrally-located city in Iran, 15 years after the initiation of universal salt iodization. In total, 2,523 Isfahani adults (1,275 males, 1,248 females) aged > 20 years were selected by multi-stage cluster-sampling method. Goitre rate, serum thyroid-stimulating hormone (TSH), thyroxine ...
Mao Yu-Shan - - 2010
The prevalence and the spectrum of thyroid dysfunction in the mainland of China are not adequately understood. We performed a population-based study to determine the prevalence of major thyroid dysfunctions including overt and subclinical hyper- and hypothyroidism in a stable cohort. All active and retired employees aged 20 years and ...
Trivedi Kalyani - - 2010
To determine the hard tissue surgical cephalometric norms statistically and geometrically in well-balanced faces having clinically acceptable facial profile in the Rajasthan population. To compare the cephalometric analyses of Rajasthanis males and females and to compare the craniofacial pattern of Rajasthani population with Caucasian norms. Lateral cephalograms of 200 subjects ...
Poiani Silvana Beani - - 2010
The cephalic salivary glands of some species of bees are exclusive and well developed only in Apinae. These glands were studied with light and scanning electron microscopy in workers, queens and males from the honey bee Apis mellifera, and the stingless bee Scaptotrigona postica in different life phases. The results ...
Over Rebecca - - 2010
Some studies suggest altered pituitary functioning and TSH production with aging. Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age. We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T4 concentrations. Two populations ...
Putta-Manohar Sudeep - - 2010
Thyroid orbitopathy is a relatively rare disease. Prevalence data are lacking and can only be estimated. The incidence of thyroid orbitopathy has been documented in one American study (16 cases per 100,000 population per year for females and 2.9 cases per 100,000 population for males). Thyroid orbitopathy can affect every ...
Imani Elham Faghih - - 2010
INTRODUCTION: The aim of this study was to investigate the current status of sonographic characteristics of thyroid nodules in Isfahan, a previously iodine deficient area in central Iran. MATERIAL AND METHODS: In a cross-sectional study conducted in 2006, 2523 adult people (age > 20 years) were selected by a multistage ...
Su Pen-Hua - - 2010
Because placental polychlorinated dibenzo-p-dioxins,dibenzofurans (PCDD/Fs) levels are associated with decreased free thyroxine (FT(4)) and thyroid stimulating hormone (TSH) in neonates, we assessed development by gender and maternal PCDD/Fs exposure at years 2 and 5 in 92 mother and newborn pairs. RIA quantified thyroid, sex, and growth hormones. Of 200 subjects ...
de Freitas Clarice Umbelino - - 2010
BACKGROUND: Based on a suspicion raised by a health professional and due to a subsequent legal request, a cross-sectional study was made with a comparison group to investigate a possible excess of Hashimoto's thyroiditis-HT and antibodies-ATA in the surroundings of a Petrochemical Complex. METHODS: People of both sexes aged over ...
Keles Mustafa - - 2010
The purpose of this study was to evaluate the alterations in salivary gland function in patients who receiving continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure (CRF) using technetium-99m pertechnetate ((99m)Tc-P) salivary gland scintigraphy. The study population consisted of 36 CAPD patients (16 males and 20 females, ranging in ...
Ceresini Graziano - - 2010
Subclinical thyroid disease (STD) is defined as circulating concentrations of free T4 and free T3 within their respective reference ranges in the presence of abnormal circulating concentrations of TSH. SCD is being diagnosed more frequently in clinical practice and is reported to be more prevalent in elderly as compared to ...
Jafarzadeh Abdollah - - 2010
It has been reported that the immune system undergoes age and gender changes. The aim of this study was to investigate the age- and gender-dependent changes of salivary IgA and IgE levels among healthy subjects. A total of 203 healthy individuals (aged 1-70 years) were enrolled in the study. Two ...
Molecular evaluation of the human gut methanogenic archaeal microbiota reveals an age-associated ...
Mihajlovski Agnès - - 2010
The methanogenic diversity of the human intestinal microbiota has long been viewed as composed of two Methanobacteriales: Methanobrevibacter smithii and Methanosphaera stadtmanae. Recently, Mx-01, a new phylotype hypothesized to belong to a putative sixth methanogenic order, was recovered from human faeces. Here we examined the diversity and the distribution of ...
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text:
Page 1
BioMed Central
Page 1 of 9
(page number not for citation purposes)
Journal of Translational Medicine
Open Access
Non-expanded adipose stromal vascular fraction cell therapy for
multiple sclerosis
Neil H Riordan1, Thomas E Ichim*1, Wei-Ping Min2, Hao Wang2,
Fabio Solano3, Fabian Lara3, Miguel Alfaro4, Jorge Paz Rodriguez5,
Robert J Harman6, Amit N Patel7, Michael P Murphy8, Roland R Lee9,10 and
Boris Minev11,12
Address: 1Medistem Inc, San Diego, CA, USA, 2Department of Surgery, University of Western Ontario, London, Ontario, Canada, 3Cell Medicine
Institutes, San Jose, Costa Rica, 4Hospital CIMA, San Jose, Costa Rica, 5Cell Medicine Institutes, Panama City, Panama, 6Vet-Stem, Inc. Poway, CA,
USA, 7Dept of Cardiothoracic Surgery, University of Utah, Salt Lake City, Utah, USA, 8Division of Medicine, Indiana University School of Medicine,
Indiana, USA, 9Department of Radiology, University of Canlfornia San Diego, San Diego, CA, USA, 10Veterans Administration, San Diego, CA,
USA, 11Moores Cancer Center, University of California, San Diego, CA, USA and 12Department of Medicine, Division of Neurosurgery, University
of California San Diego, San Diego, CA, USA
Email: Neil H Riordan - firstname.lastname@example.com; Thomas E Ichim* - email@example.com; Wei-Ping Min - firstname.lastname@example.com;
Hao Wang - email@example.com; Fabio Solano - firstname.lastname@example.com; Fabian Lara - firstname.lastname@example.com;
Miguel Alfaro - firstname.lastname@example.com; Jorge Paz Rodriguez - firstname.lastname@example.com; Robert J Harman - email@example.com;
Amit N Patel - firstname.lastname@example.com; Michael P Murphy - firstname.lastname@example.com; Roland R Lee - firstname.lastname@example.com;
Boris Minev - firstname.lastname@example.com
* Corresponding author
The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells
(MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory
M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of
this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose
derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects
of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have
been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of
these cells for systemic immune modulation has not been reported. In this communication we
discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our
experiences with three patients. Based on this rationale and initial experiences, we propose
controlled trials of autologous SVF in various inflammatory conditions.
1. Introduction
Adipose tissue has attracted interest as a possible alterna-
tive stem cell source to bone marrow. Enticing character-
istics of adipose derived cells include: a) ease of
extraction, b) higher content of mesenchymal stem cells
(MSC) as compared to bone marrow, and c) ex vivo
expandability of MSC is approximately equivalent, if not
superior to bone marrow [1]. With one exception [2], clin-
ical trials on adipose derived cells, to date, have been lim-
ited to ex vivo expanded cells, which share properties with
bone marrow derived MSC [3-8]. MSC expanded from
adipose tissue are equivalent, if not superior to bone mar-
Published: 24 April 2009
Journal of Translational Medicine 2009, 7:29doi:10.1186/1479-5876-7-29
Received: 16 March 2009
Accepted: 24 April 2009
This article is available from: http://www.translational-medicine.com/content/7/1/29
© 2009 Riordan et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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row in terms of differentiation ability [9,10], angiogenesis
stimulating potential [11], and immune modulatory
effects [12]. Given the requirements and potential con-
taminations associated with ex vivo cellular expansion, a
simpler procedure would be the use of primary adipose
tissue derived cells for therapy. Indeed it is reported that
over 3000 horses with various cartilage and bone injuries
have been treated with autologous lipoaspirate fractions
without cellular expansion [13]. In double blind studies
of canine osteoarthritis statistically significant improve-
ments in lameness, range of motion, and overall quality
of life have been described [14,15].
If such approaches could be translated clinically, an easy-
to-use autologous stem cell therapy could be imple-
mented that is applicable to a multitude of indications.
Indeed, this is the desire of commercial entities that are
developing bench top closed systems for autologous adi-
pose cell therapy, such as Cytori's Celution™ system [16]
and Tissue Genesis' TGI 1000™ platform [17], which are
presently entering clinical trials. Unfortunately, since the
majority of scientific studies have focused on in vitro
expanded adipose derived cells, relatively little is known
about the potential clinical effects of the whole lipoaspi-
rate that contains numerous cell populations besides
MSC. From a safety perspective the process of autologous
fat grafting has been commonly used in cosmetic surgery
[18,19], so at least theoretically, autologous cell therapy,
with the numerous cellular populations besides MSC that
are found in adipose tissue, should be relatively innocu-
ous. However, from an efficacy or disease-impact perspec-
tive, it is important to consider the various cellular
components of adipose tissue and to develop a theoretical
framework for evaluating activities that these components
may mediate when administered systemically. For exam-
ple, while attention is focused on the MSC component of
adipose tissue, the high concentrations of monocytes/
macrophages, and potential impact these may have on a
clinical indication is often ignored.
In this paper we will discuss the potential use of the adi-
pose derived cells for the treatment of inflammatory con-
ditions in general, with specific emphasis on multiple
sclerosis. Due to the chronic nature of the disease, the fact
that in some situations remission naturally occurs, as well
as lack of therapeutic impact on long term progression of
current treatments, we examine the possibility of using
autologous adipose derived cells in this condition. We
will discuss the cellular components of adipose tissue, the
biology of these components, how they may be involved
in suppression of inflammatory/immunological aspects
of MS, and conclude by providing case reports of three
patients treatment with autologous adipose derived cells.
2. Components of Adipose Tissue
Mesenchymal Stem Cells
The mononuclear fraction of adipose tissue, referred to as
the stromal vascular fraction (SVF) was originally
described as a mitotically active source of adipocyte pre-
cursors by Hollenberg et al. in 1968 [20]. These cells mor-
phologically resembled
demonstrated to differentiate into pre-adipocytes and
functional adipose tissue in vitro [21]. Although it was
suggested that non-adipose differentiation of SVF may
occur under specific conditions [22], the notion of "adi-
pose-derived stem cells" was not widely recognized until
a seminal paper in 2001, where Zuk et al demonstrated
the SVF contains large numbers of mesenchymal stem
cells (MSC)-like cells that could be induced to differenti-
ate into adipogenic, chondrogenic, myogenic, and osteo-
genic lineages [23]. Subsequent to the initial description,
the same group reported after in vitro expansion the SVF
derived cells had surface marker expression similar to
bone marrow derived MSC, comprising of positive for
CD29, CD44, CD71, CD90, CD105/SH2, and SH3 and
lacking CD31, CD34, and CD45 expression [24]. Boquest
et al characterized fresh CD45 negative, CD34 positive,
CD105 positive SVF cells based on CD31 expression. They
demonstrated that the CD31 negative cells exhibited mes-
enchymal properties and could be expanded in vitro,
whereas the CD31 positive cells possessed endothelial-
like properties with poor in vitro expansion capacity [25].
Mesenchymal cells with pluripotent potential have also
been isolated from the liposuction aspirate fluid, which is
the fluid portion of liposuction aspirates [26].
fibroblasts and were
Endothelial Progenitor Cells
In addition to MSC content, it was identified that SVF con-
tains endothelial precursor cells (EPC). A common notion
is that vasculature tissue continually replenishes damaged
endothelial cells de novo from circulating bone marrow
derived EPC [27], and that administration of exogenous
EPC in animals having damaged vasculature can inhibit
progression of atherosclerosis or restenosis [28,29].
Miranville et al demonstrated that human SVF cells iso-
lated from subcutaneous or visceral adipose tissue contain
a population of cells positive for CD34, CD133 and the
drug efflux pump ABCG2 [30]. These cells had endothe-
lial colony forming ability in vitro, and in vivo could
induce angiogenesis in a hindlimb ischemia model. Inter-
estingly, the concentrations of cells with the phenotype
associated with in vivo angiogenic ability, CD31 negative
and CD34 positive, was positively associated with body
mass index. This suggests the possibility that endothelial
precursor cell entrapment in adipose tissue of obese
patients may be related to the reduced angiogenic func-
tion seen in obesity [31]. Several other groups have
reported CD34 positive cells in the SVF capable of stimu-
lating angiogenesis directly or through release of growth
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factors such as IGF-1, HGF-1 and VEGF [32-35]. The exist-
ence of a CD34 positive subset in the SVF may indicate
possibility of cells with not only endothelial but also
hematopoietic potential. Indeed at least one report exists
of a bipotent hematopoietic and angiopoietic phenotype
isolated from the SVF [36]. Thus from these data it appears
that SVF contains at least 2 major populations of stem
cells, an MSC compartment and an EPC compartment
that may have some hematopoietic activity. When these
cells are quantified, one author describes that from pri-
mary isolated SVF, approximately 2% of the cells have the
hematopoietic-associated CD34+ CD45+ phenotype, and
6.7% having a mesenchymal CD105+ CD146+ pheno-
type [37]. Many studies using SVF perform in vitro expan-
sion of the cells, this causes selection for certain cell
populations such as MSC and decreases the number of
CD34 cells [38]. Thus in vitro expanded SVF derived cells
can not be compared with primary isolated SVF cells.
Immune Regulatory Monocytes/Macrophages
In addition to its stem/progenitor cell content, the SVF is
known to contain monocytes/macrophages. Although
pluripotency of monocytic populations has previously
been described [39,40], we will focus our discussion to
immunological properties. Initial experiments suggested
that macrophage content of adipose tissue was associated
with the chronic low grade inflammation found in obese
patients. This was suggested by co-culture experiments in
which adipocytes were capable of inducing TNF-alpha
secretion from macrophage cell lines in vitro [41]. Clinical
studies demonstrated that adipocytes also directly release
a constitutive amount of TNF-alpha and leptin, which are
capable of inducing macrophage secretion of inflamma-
tory mediators [42]. It appears from several studies in
mice and humans that when monocytes/macrophages are
isolated from adipose tissue, they in fact possess anti-
inflammatory functions characterized by high expression
of IL-10 and IL-1 receptor antagonist [43-45]. These adi-
pose derived macrophages have an "M2" phenotype,
which physiologically is seen in conditions of immune
suppression such as in tumors [46], post-sepsis compen-
satory anti-inflammatory syndrome [47,48], or pregnancy
associated decidual macrophages [49]. It is estimated that
the monocytic/macrophage compartment of the SVF is
approximately 10% based on CD14 expression [37].
Interestingly, administrations of ex vivo generated M2
macrophages have been demonstrated to inhibit kidney
injury in an adriamycin-induced model [50]. In the con-
text of MS, alternatively activated, M2-like microglial cells
are believed to inhibit progression in the EAE model [51].
Thus the anti-inflammatory activities of M2 cells are a
potential mechanism of therapeutic effect of SVF cells
when isolated from primary sources and not expanded.
T Regulatory Cells
It has been reported by us and others, that activation of T
cells in the absence of costimulatory signals leads to gen-
eration of immune suppressive CD4+ CD25+ T regulatory
(Treg) cells [52,53]. Thus local activation of immunity in
adipose tissue would theoretically be associated with
reduced costimulatory molecule expression by the M2
macrophages, which theoretically may predispose to Treg
generation. Conversely, it is known that Tregs are
involved in maintaining macrophages in the M2 pheno-
type [54]. Supporting the possibility of Treg in adipose tis-
sue also comes from the high concentration of local MSC
which are known to secrete TGF-beta [55] and IL-10 [56],
both involved in Treg generation [57]. Indeed numerous
studies have demonstrated the ability of MSC to induce
Treg cells [56,58-60]. To test the possibility that Treg exist
in the SVF, we performed a series of experiments isolating
CD4, CD25 positive cells from the SVF of BALB/c mice
and compared frequency between other tissues, (lymph
node and spleen). We observed a 3 fold increase in the
CD4+, CD25+ compartment as compared to control tis-
sues. Functionally, these cells were capable of suppressing
ConA stimulated syngeneic CD4+ CD25+ negative cells
(manuscript in preparation).
3. Treatment of Autoimmunity with Adipose
In general, MSC, whether derived from the bone marrow,
adipose, or other sources, have been demonstrated to
exert dual functions that are relevant to autoimmunity
[61-65]. These conditions are usually exemplified by acti-
vation of innate immune components, breakdown of self
tolerance of the adaptive immune response, and subse-
quent destruction of tissues. Although these are generali-
zations, an initial insult either by foreign microorganisms,
or other means, causes tissue damage and activation of
innate immunity, which under proper genetic back-
ground leads to re-activation/escape from anergy of "self"-
recognizing T cell clones, thus causing more tissue dam-
age, activation of immunity, and lose of function. MSC
inhibit innate immune activation by blocking dendritic
cell maturation [66,67], by suppressing macrophage acti-
vation [68], and by producing agents such as IL-1 receptor
antagonist [69] and IL-10 [70] that directly block inflam-
matory signaling. Perhaps the strongest example of MSC
inhibiting the innate immune response is the recent pub-
lication of Nemeth et al, which demonstrated that admin-
istration of MSC can block onset of sepsis in the aggressive
cecal ligation and puncture model [68]. Through inhibit-
ing DC activation, MSC suppress subsequent adaptive
immunity by generating T regulatory (Treg) cells [59], as
well as blocking cytotoxic activities of CD8 cells. In some
situations, increased immunoregulatory activity is
reported with expanded MSC compartment of SVF as
reported by Mcintosh et al. [71].
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In addition to inhibiting pathological innate and adaptive
immunity, MSC have the ability to selectively home to
areas of tissue damage, and mediate direct or indirect
repair function. As an example, CXCR-4 expression of
MSC allows homing toward injured/hypoxic tissue after
intravenous administration. Indeed this has allowed for
numerous studies demonstrating positive effects of intra-
venously administered MSC causing regeneration in
many tissues such as CNS injury [72,73], transplant rejec-
tion [59], toxin-induced diabetes [74], nephropathy [75],
and enteropathy [76]. The regenerative effects of MSC
have been postulated to be mediated by differentiation
into damaged tissue, although this is somewhat contro-
versial, as well as through secretion of growth factors/
antiapoptotic factors which induce tissue regeneration
The ability of MSC to inhibit immune response, while
offering the possibility of inducing/accelerating healing of
tissue that has already been damaged, makes this popula-
tion attractive for treatment of autoimmune disorders.
While numerous studies clinical studies are using
expanded MSC derived from the bone marrow [79-81],
here we chose an indication of autologous adipose SVF
based on the immunological profile, the length of disease
progress allowing several interventions, and the fact that
the disease naturally has periods of remission during
which the rationale would be to amplify a process that
already is underway.
4. Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune condition in
which the immune system attacks the central nervous sys-
tem (CNS), leading to demyelination. It may cause
numerous physical and mental symptoms, and often
progresses to physical and cognitive disability. Disease
onset usually occurs in young adults, and is more com-
mon in women [82]. MS affects the areas of the brain and
spinal cord known as the white matter. Specifically, MS
destroys oligodendrocytes, which are the cells responsible
for creating and maintaining the myelin sheath, which
helps the neurons carry electrical signals. MS results in a
thinning or complete loss of myelin and, less frequently,
transection of axons [83].
Current therapies for MS include steroids, immune sup-
pressants (cyclosporine, azathioprine, methotrexate),
immune modulators (interferons, glatiramer acetate), and
immune modulating antibodies (natalizumab). At
present none of the MS treatment available on the market
selectively inhibit the immune attack against the nervous
system, nor do they stimulate regeneration of previously
damaged tissue.
Treg cells modulate MS
Induction of remission in MS has been associated with
stimulation of T regulatory cells. For example, patients
responding to the clinically used immune modulatory
drug glatiramer acetate have been reported to have
increased levels of CD4+, CD25+, FoxP3+ Treg cells in
peripheral blood and cerebral spinal fluid [84]. Interferon
beta, another clinically used drug for MS induces a renor-
malization of Treg activity after initiation of therapy
through stimulation of de novo regulatory cell generation
[85]. In the animal model of MS, experimental allergic
encephalomyelitis (EAE), disease progression is exacer-
bated by Treg depletion [86], and natural protection
against disease in certain models of EAE is associated with
antigen-specific Treg [87]. Thus there is some reason to
believe that stimulation of the Treg compartment may be
therapeutically beneficial in MS.
Endogenous neural stem cells affect MS recovery
In addition to immune damage, MS patients are known to
have a certain degree of recovery based on endogenous
repair processes. Pregnancy associated MS remission has
been demonstrated to be associated with increased white
matter plasticity and oligodendrocyte repair activity [88].
Functional MRI (fMRI) studies have suggested that vari-
ous behavioral modifications may augment repair proc-
esses at least in a subset of MS patients [89]. Endogenous
stem cells in the sub-ventricular zone of brains of mice
and humans with MS have been demonstrated to possess
ability to differentiate into oligodendrocytes and to some
extent assist in remyelination [89]. For example, an 8-fold
increase in de novo differentiating sub-ventricular zone
derived cells was observed in autopsy samples of MS
patients in active as compared to non-active lesions [90].
Stem Cell Therapy for MS
The therapeutic effects of MSC in MS have been demon-
strated in several animal studies. In one of the first studies
of immune modulation, Zappia et al. demonstrated
administration of MSC subsequent to immunization with
encephalomyelitis-inducing bovine myelin prevented
onset of the mouse MS-like disease EAE. The investigators
attributed the therapeutic effects to stimulation of Treg
cells, deviation of cytokine profile, and apoptosis of acti-
vated T cells [73]. It is interesting to note that the MSC
were injected intravenously. Several other studies have
shown inhibition of EAE using various MSC injection pro-
tocols [91,92].
To our knowledge there is only one publication describ-
ing clinical exploration of MSC in MS. An Iranian group
reported using intrathecal injections of autologous culture
expanded MSC in treatment unresponsive MS patients
demonstrated improvement in one patient (EDSS score
from 5 to 2.5), no change in 4 patients, and progressive
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disease in 5 patients based on EDSS score. Functional sys-
tem assessment revealed six patients had improvement in
their sensory, pyramidal, and cerebellar functions. One
showed no difference in clinical assessment and three
deteriorated [93].
5. Case Reports
Given the rationale that autologous SVF cells have a rea-
sonable safety profile, and contain both immune modu-
latory and regenerative cell populations, a physician-
initiated compassionate-use treatment was explored in 3
patients. Here we describe their treatments and histories.
In 2005, a 50-year-old man was diagnosed with Relaps-
ing-remitting MS, presenting with tonic spasms, stiffness,
gait imbalance, excessive hearing loss, loss of coordina-
tion, numbness in both feet, sexual dysfunction, severe
pain all over his body, fatigue and depression. In 2005,
the patient experienced refractory spells of tonic flexion
spasms, occurring for several minutes at a time and multi-
ple times throughout the day. He was treated with muscle
relaxants, I.V. steroids and Tegretol, and his condition had
improved. However, in 2006 he experienced severe
uncontrollable tonic extensions of all four extremities
lasting about two minutes and associated with significant
pain. Cranial MRI done at that time revealed at least 30
periventricular white matter lesions. Patient also reported
excellent response to Solu-Medrol infusions. Therefore,
the combination of response to steroids, characteristic
MRI abnormalities and positive oligoclonal banding
strongly suggested a diagnosis of Relapsing Remitting MS.
Infusions of Tysabri (Natalizumab, Biogen Idec) every
four weeks were prescribed in November 2006, with excel-
lent results and no significant side effects. However, in
March 2007 patient reported spasticity approximately
three weeks after the infusions, leading to alteration of his
Tysabri infusion regimen to Q3 weeks. By June 2007 the
patient had began complaining of significant memory
loss and by September 2007 he has had recurrence of his
tonic spasms with multiple attacks daily. He was treated
with Solu-Medrol, Baclofen, Provigil, Tegretol, Trileptal,
Tysabri, Vitamins, Omega-3 and Zanaflex with some
improvement of his neurologic symptoms. However, he
complained of severe abdominal pain, decreased appetite
and melanotic stools, consistent with stress ulcer second-
ary to steroid treatment. By November 2007 the patient
was still somewhat responsive to Tysabri and I.V. Solu-
Medrol, but continued to experience multiple severe tonic
spasms at a rate of 30 – 40 spasms per month.
In May 2008, the patient was treated with two I.V. infu-
sions of 28 million SVF cells and multiple intrathecal and
intravenous infusions of allogeneic CD34+ and MSC cells.
MSC were third party unmatched and CD34 were
matched by mixed lymphocyte reaction. Infusions were
performed within a 9-day period and were very well toler-
ated without any adverse or side effects. No other treat-
ments were necessary during the patient's stay. After the
second stem cell infusion the patient reported a signifi-
cant decrease of his generalized pain. However, he contin-
ued to experience severe neck and shoulder pain and was
re-evaluated by his neurologist. Two months after the
stem cell therapy, the volume of his hearing aids had to be
lowered once per week over 4 weeks. Three months after
the stem cell infusions the patient reported a significant
improvement of his cognition and almost complete
reduction of the spasticity in his extremities. He men-
tioned that he has had 623 tonic seizures in the past and
confirmed that he has not experienced any more seizures
since the completion of the stem cell therapy. A neurolog-
ical evaluation performed three months after the stem cell
infusions revealed an intact cranial nerve (II-XII) function
and no nystagmus, normal motor function without any
atrophy or fasciculations, and intact sensory and cerebel-
lar functions and mental status. New MRI images,
obtained 6 months after the stem cell treatment showed
lesions, very similar to the lesions observed before the
stem cell treatment (Figure 1). The patient also reported
significantly improved memory, sexual function, and
energy level. Currently, the patient is taking only multivi-
tamin, minerals and Omega 3.
Second patient: A 32-year-old man was diagnosed in 2001
with relapsing-remitting MS, presenting with fatigue and
depression, uneven walk pattern, cognitive dysfunction,
and a progressive decline in his memory without any spe-
cific neurological symptoms. In 2002 he was started on
weekly intramuscular Avonex (IFN-b1a, Biogen Idec) and
has had no further exacerbations and no evidence of pro-
gressive deterioration. Patient's fatigue was treated well
with Provigil, and his mood improved significantly due to
treatment with Wellbutrin SR. In 2007, the patient com-
plained of some mood changes, with more agitation, irri-
tability, mood destabilization, and cognitive slowing. As
depression was suspected in playing a central role in
patient's condition, Razadyne was added to the antide-
pressant regimen.
In 2008, the patient was treated with two I.V. infusions of
25 million autologous adipose-derived SVF cells and mul-
tiple intrathecal and intravenous infusions of allogeneic
CD34+ and MSC cells. MSC were third party unmatched
and CD34 were matched by mixed lymphocyte reaction.
All infusions were performed within a 10-day period and
were very well tolerated without any significant side
effects. The treatment plan also included physical therapy
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MRI Images obtained before (Panels A and B), and six months after (Panel C) the stem cell treatment of patient 1
Figure 1
MRI Images obtained before (Panels A and B), and six months after (Panel C) the stem cell treatment of
patient 1. Panels A and B: Consecutive axial FLuid-Attenuated Inversion Recovery (FLAIR) images through the lateral ven-
tricles show multiple small foci of bright signal in the periventricular and subcortical white matter, consistent with plaques of
multiple sclerosis. Panel C: Axial FLAIR image shows no significant change in the multiple periventricular and subcortical
white-matter plaques. (For the comparison, note that this slice is positioned between those in A and B, and at slightly different
scanning-angle, so it includes lesions of both those slices, as well as others slightly out-of their plane.).
MRI Images obtained before (Panels A and B), and seven months after (Panel C) the stem cell treatment of patient 2
Figure 2
MRI Images obtained before (Panels A and B), and seven months after (Panel C) the stem cell treatment of
patient 2. Panels A and B: Consecutive axial FLuid-Attenuated Inversion Recovery (FLAIR) images through the lateral ven-
tricles show multiple small patches of bright signal in the periventricular and subcortical white matter, consistent with plaques
of multiple sclerosis. Panel C: Axial FLAIR image shows no significant change in the multiple periventricular and subcortical
white-matter plaques. (For the comparison, note that this slice is positioned similar to slice A but at slightly different scanning-
angle, so it includes lesions of both slices A and B.).
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Three months after the stem cell infusions the patient
reported a significant improvement of his balance and
coordination as well as an improved energy level and
mood. New MRI images, obtained 7 months after the
stem cell treatment showed lesions, very similar to the
lesions observed before the stem cell treatment (Figure 2).
Currently, he is not taking any antidepressants and is
reporting a significantly improved overall condition. His
current treatment regiment includes a weekly injection of
Avonex, vitamins, minerals and Omega 3.
The patient was diagnosed with relapsing-remitting MS in
1993, presenting symptoms were noticeable tingling and
burning sensation in the right leg, followed by paraplegia
lasting almost three weeks. Neurological investigations at
the time uncovered MRI findings suggestive for a demyeli-
nating syndrome. In June of 2008, the patient was treated
with two I.V. infusions of 75 million autologous adipose-
derived SVF cells and multiple intrathecal and intrave-
nous infusions of allogeneic CD34+ and MSC cells. MSC
were third party unmatched and CD34 were matched by
mixed lymphocyte reaction. All infusions were performed
within a 10-day period and were very well tolerated with-
out any significant side effects. His gait, balance and coor-
dination improved dramatically oven a period of several
weeks. His condition continued to improve over the next
few months and he is currently reporting a still continuing
improvement and ability to jog, run and bike for extended
periods of time daily.
The patients treated were part of a compassionate-use
evaluation of stem cell therapeutic protocols in a physi-
cian-initiated manner. Previous experiences in MS
patients using allogeneic CD34+ cord blood cells together
with MSC did not routinely result in substantial improve-
ments observed in the three cases described above. While
obviously no conclusions in terms of therapeutic efficacy
can be drawn from the above reports, we believe that fur-
ther clinical evaluation of autologous SVF cells is war-
ranted in autoimmune conditions.
Competing interests
Thomas E Ichim and Neil H Riordan are management and
shareholders of Medistem Inc, a company that has filed
intellectual property on the use of adipose stromal vascu-
lar fraction cells for immune modulation.
Authors' contributions
All authors read and approved the final manuscript. NHR,
TEI, WPM, HW, FS, FL, MA, JPR, RJH, ANP, MPM, RRL and
BM conceived experiments, interpreted data, and wrote
the manuscript.
We thank Victoria Dardov, Rosalia De Necochea Campion, Florica Batu,
and Boris Markosian for stimulating discussions.
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Gronthos S: Multipotential human adipose-derived stromal
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Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi
K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek
I, Star RA, Mezey E: Bone marrow stromal cells attenuate sep-
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DG: Interleukin 1 receptor antagonist mediates the antiin-
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McIntosh K, Zvonic S, Garrett S, Mitchell JB, Floyd ZE, Hammill L,
Kloster A, Di Halvorsen Y, Ting JP, Storms RW, Goh B, Kilroy G, Wu
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Mishra PK: Bone marrow-derived mesenchymal stem cells for
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Pittock SJ, Lucchinetti CF: The pathology of MS: new insights
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CD4(+)CD25(+) T cells exacerbates experimental autoim-
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Report of a pilot study. Iran J Immunol 2007, 4:50-57.

subset: commoncrawl


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Nerlens Noel
Posted on: Thu, 02/14/2013 at 3:45pm
Nerlens Noel
Why do some feel he's going back to school?????
Why would he go back to school and take the chance of getting hurt AGAIN????
I could see if he was a 6'2 guard, but he's a legit 7'0 Center, a team is going to take a chance on him and he's only 18, he will recover and heal and be back to his old self possibly better.


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Every year, more than 3,000 scientific abstracts are accepted for oral and poster presentation at the Society's annual meeting.
Urge Congress to find a balanced approach to deficit reduction that does not involve further cuts to biomedical research
Published on: March 01, 2012
Drs. Byrd and Johnson indicated no relevant conflicts of interest.
Ponader S, Chen S, Buggy JJ, et al. Bruton's tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2011. Epub ahead of print.
A common finding in chronic lymphocytic leukemia (CLL) patients is constitutive activation of kinases associated with the B-cell receptor (BCR) signaling pathway. Several small-molecule inhibitors including GS-1101 that target Syk (splenic tyrosine kinase) and PCI-32765 that target BTK (Burton agammaglobulinemia tyrosine kinase) showed potential efficacy in preclinical testing based on their capacity to inhibit BCR signaling. These agents subsequently entered the clinical arena, and early experience indicated that they were ineffective in treating CLL based on worsening of peripheral blood lymphocytosis. Extended follow-up, however, proved otherwise. In some treated patients, lymphocytosis returned to pre-treatment baseline values, but more importantly, durable reduction in lymph node and spleen involvement and improvement in cytopenias was observed despite persistent lymphocytosis. In the current study, a collaborative effort involving the laboratories of Nicholas Chiorazzi (Feinstein Institute for Medical Research) and Jan Burger (MD Anderson Cancer Center), the mechanisms of action of PCI-32765 were investigated using both in vitro and in vivo models. PCI-32765 is an irreversible BTK inhibitor1 that has anti-apoptotic and anti-proliferative properties against CLL cells independent of microenvironment signals.2 This new paper extends the observation of the initial study by showing that CLL cell migration, proliferation on stromal cells, and adhesion are altered by PCI-32765 in vitro. Evidence of disrupted signaling is demonstrated in vivo in CLL patients, where plasma levels of the BCR-dependent chemokines CCL3 and CCL4 are rapidly reduced following initiation of PCI-32765 treatment. To study the effects of PCI-32765 in vivo, an adoptive transplant model was used.3 The particular TCL1 murine leukemia cells used in this system (TCL-192) were selected in part because they express a BCR that is reactive with phosphatidylcholine. Compared with mice treated with the vehicle control, PCI-32765-treated mice engrafted with TCL1 cells developed lymphocytosis initially; however, reduction in disease and improvement in overall survival were subsequently observed. Concordantly, inhibition of downstream BTK-activated targets was demonstrated.
Why are these results important? The inhibitors of BCR signaling are active in CLL, yet their effects on lymphocyte trafficking challenge our traditional way of assessing disease response in which finding an increase in lymphocytosis is seen as an indication of disease progression. PCI-32765-induced lymphocytosis appears to be a consequence of aberrant trafficking in which movement into compartments outside of the peripheral blood system is inhibited. Therefore, PCI-32765-induced lymphocytosis likely results from cellular redistribution rather than clonal expansion. The studies of Ponader et al. have expanded our understanding of the effects of inhibition of BCR signaling kinases on the properties of CLL cellsin vitro. Importantly, their adoptive transplant system appears to be a valid model for investigating the effects of these inhibitors in vivo. By incorporating use of genetically modified TCL1 cells, this model provides a tool for future studies aimed at teasing out the precise mechanisms by which inhibitors of BCR signaling kinases modulate lymphocyte trafficking. The inhibitors of BCR signaling kinases are an exciting new class of drugs for treatment of CLL, and the studies of Ponader and colleagues and others build upon our knowledge of how these agents work.
Urge Congress to find a balanced approach to deficit reduction that does not involve further cuts to biomedical research.
September 17-19, 2015 Fairmont Chicago, Millennium ParkChicago, IL
ASH, the leading authority on malignant hematology, presents its newest clinical meeting.


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WFP Executive Director Meets Survivors Of Typhoon Haiyan
"What I've seen in Tacloban today is the incredible resilience of the Filipino people. These people are not asking for a handout, they're asking for a hand up to rebuild their lives," Erharin Cousin said, after helping to distribute High Energy Biscuits to children at a local high school that has been turned into an evacuation centre. DONATE NOW
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ASOT podcast awaits you with a Mirage-special
Only a few days after the official release of Armin van BuurenŌĆÖs ŌĆśMirageŌĆÖ, the DJ has another special surprise in stores for you. Every week, he selects his favorite tunes of the A State of Trance radio show to puts them into his official Podcast. This weekŌĆÖs edition awaits you with an exclusive ŌĆśMirage SpecialŌĆÖ and brings you five completely new productions, straight from the bonus edition of the ŌĆśMirageŌĆÖ album to your speakers, and all of that – for free!
The orchestral masterpiece of title track ŌĆśMirageŌĆÖ, the housy ŌĆśDrowningŌĆÖ feat. Laura V and euphoric vocal collab ŌĆśI SurrenderŌĆÖ with Cathy Burton are part of this episode, that also showcases the atmospheric instrumental ŌĆśOrbionŌĆÖ and last but definitely not least lovely ŌĆśDown To LoveŌĆÖ with rising star Ana Criado. Check out the latest ASOT Podcast on iTunes or ArminŌĆÖs official YouTube Channel!


text:
The Internet of Things is coming. Some might say it's already here.
Don't rush into a new home without a thorough inspection
Join the NASDAQ Community today and get free, instant access to portfolios, stock ratings, real-time alerts, and more!
On Jan 16, we maintained our Neutral recommendation on Rogers Communications Inc. ( RCI ). In the recently concluded third quarter fiscal 2013, the company missed both the top and bottom line of the Zacks Consensus Estimate.
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FDA Approves Tretten to Treat Rare Genetic Clotting Disorder »
"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
Read the FDA Approves Tretten to Treat Rare Genetic Clotting Disorder article »
Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 1-[5[(aminoiminomethyl)amino]1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl]amino]pentyl]-4methyl-2-piperidinecarboxylic acid, monohydrate. Argatroban has 4 asymmetric carbons. One of the asymmetric carbons has an R configuration (stereoisomer Type I) and an S configuration (stereoisomer Type II). Argatroban consists of a mixture of R and S stereoisomers at a ratio of approximately 65:35.
The molecular formula of argatroban is C23H36N6O5S•H2O. Its molecular weight is 526.66 g/mol. The structural formula is:
Argatroban Injection is a sterile, non-pyrogenic, clear, colorless to pale yellow isotonic solution. It is supplied in a single use polyolefin bag containing 250 mg of argatroban in 250 mL sodium chloride solution (1 mg/mL). Each mL contains 1 mg argatroban, 9 mg sodium chloride, USP, and 3 mg sorbitol, NF in water for injection, USP. The pH of the solution is between 3.2 to 7.5.
What are the possible side effects of argatroban (Acova)?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect such as:
- feeling like you might pass out;
- easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
- blood in your urine;
- black, bloody, or tarry stools;
- coughing up blood or vomit that looks like coffee grounds;
- any bleeding that will not stop;
- pain or...
Read All Potential Side Effects and See Pictures of Argatroban »
What are the precautions when taking argatroban injection (Argatroban)?
Consult your...
Last reviewed on RxList: 12/30/2014
This monograph has been modified to include the generic and brand name in many instances.
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Gibsons RV Resort
British Columbia
Phone: (604) 989-7275
Visit Campground Website
Sites: 63
Recent Rate: $39 2/2014
Latitude: 49.4239178096264
Longitude: -123.518784710087
These reviews are the opinion of an RVParkReviews' member and not the views of RVParkReviews.com
Date of Stay: February, 2014 - $39.00
Office is located in the first unit on the left as you pull in. The woman was very friendly, but forgot to give us the cable box for the cable TV, and seemed confused about the new internet sign on procedures. On the whole the park was well kept, in spite of a lot of full time residents, except for a burnt out car which was almost blocking one part of the road. There is no real designated dog area, but there is a wooded area next to the park, a children's playground, pay laundry and only 2 pay showers for the entire park. All the sites are very large but gravel, and were a little muddy since a layer of snow had just melted. We found the night to be extremely quiet. We would stay here again. We camped at Gibsons RV Resort in a Travel Trailer.
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In honor of Walter Gaschott, US Army - Served in World War IIHometown: Whitestone, New York (Submitted August 21, 2008 by Nancy Gaschott)
My dad served during World War II with the Army's "Big Red One." Although he rarely talked about his service, our summer vacations were spent exclusively visiting one army buddy or other throughout the northeast. They fought in North Africa and Italy before preparing in England for the D-Day invasion. My dad's unit landed at Omaha Beach at 6:30 on the morning of D-Day. He remembered taking cover behind sand dunes and later how difficult the hedgerows of Normandy were to navigate around. He spent the last phases of the war in Belgium and finally Czechoslovakia.
When he came home he married a neighborhood girl who had loved him since they were children and settled into factory work, fishing on weekends and raising a family -- a kind, generous, gentle man: my hero.
Click here to return to the Vote in Honor of a Veteran Tribute Gallery


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Basically all I've ever recorded on is a MOTU interface.
Im interested in upgrading to a nice mixer.
One with better preamps and abit better to look at ! ha
The thing I dont understand is, if I was to buy an analog or a digital mixer, how would I then connect them to my pc?
Iv been looking at some pics of some on ebay etc and they dont have USB/FIREWIRE outputs (which is what iv only ever recorded on).
Can you also explain how I would benefit from having a mixer rather than an interface.
My knowledge of mixers is extremely vague as Iv never really used one.
Some mixers come with EQ/fades etc.
If i recorded something, then eq'd on the desk then exported, would those eq settings take effect, or would I still need to use eq on my DAW. Basically are the faders, eq's just for creating a mix to listen back to, not to actually mix the record?
As much info as possible wil be extremely helpfull!
Remember, Iv NEVER EVER used a mixing desk!
EDIT: Iv just been reading up on this yet again. Am i right in thinking I can connect say, my drum mics to the input of the mixer, then then connect the output of the mixer into my interface, then connect the output of my interface to the input of my mixer?


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Maximise power output from all reactor types
A large scale CO2 free and reliable energy supply
Some countries' energy security is challenged by the rising demand in electricity (due to the population and economic growth) and by the growing concern for the environment protection.
Nuclear power generation is part of the solution, providing at large scale a CO2 free and reliable energy supply. Nuclear energy fits perfectly within a balanced portfolio.
Alstom Nuclear Power App
Explore Alstom's Nuclear technology through our interactive app for iPad.
We have been working for 55 years in continuously improving our turbine island design and increasing the efficiency and reliability of all the main components to optimise our customers' investment, shorten our delivery time and lower the operating and maintenance costs.
Alstom can provide equipment and expertise – within your timeframe and budget. We already equip 30% of the world's nuclear power plants with our reliable turbine generator sets. Our equipment is currently in 40% of today's nuclear plants.
Close to 25% of the world's power production capacity depends on Alstom technology and services.
Our clean technologies generate electricity equivalent to the needs of around 1.2 billion homes.
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Nicolas Inn
- Continental Breakfast
- Free High-Speed Internet
TravelPod Member ReviewsNicolas Inn Rome
Best place to stay, close to the Coliseum, and the rest of central Rome. The hosts are terrific and really take care of you.
This review is the subjective opinion of a TravelPod member and not of TravelPod.com.
Historical Traveler Reviews Nicolas Inn Rome
A lengthy, but very truthful summary from experienced travellers.
Overall the Nicolas Inn is a fantastic value at almost any price. At the winter-time rates my girlfriend and I paid of 90 euros/night, it was an absolute steal.
There are only two real reasons why you, gentle reader, should *not* stay at the Nicolas Inn. If neither presents a problem for you, then read on.
1) Noise. This inn is spectacularly located for sightseers (one block equidistant from the Colosseum, the Roman Forum, the Via Cavour metro and the Piazza Venezia). You can get almost anywhere you'd want to go including the Villa Borghese or Vatican City with no more than a 15-20 minute walk or a cab ride less than 5 euros.
However, since it's location is "everywhere you want to be", the street outside is very busy at nearly all hours. As a frame of reference, I live along a major thoroughfare in Washington, DC and the noise level at home is comparable to the noise level along Via Cavour. This did not present any problem for me, as I have grown accustomed to it and can easily sleep through a train wreck. My girlfriend, who needs and uses ear-plugs at home, was smart enough to bring them with her and also had no problems whatsoever with the noise. If you are a light sleeper and are either unwilling or unable to use ear-plugs, the Nicolas Inn may not be for you.
2) The beds. I would describe them as comfortable, but not as comfortable as what you would find in a high-end major chain (e.g. Sheraton or Hilton).
I have minor back problems and the beds here were just fine for me. If you have significant or major back problems, you might want to call ahead and get an accurate description of the mattresses from one of the two main proprietors (Francois or Melissa - both of whom were extremely honest with us in all dealings). Then you can make an informed decision if the beds will be adequate for you. If you think your back might need some extra support, the Nicolas Inn may not be for you.
Other than those two considerations, this place is a definite gem. Small, owner-operated B&Bs are always a roll of the dice, but this place is a Lucky 7. A few reasons why:
- The continental breakfasts, while technically still "continental" were unusually large and varied.
- The proprietors were not only knowledgeable and immaculately professional, but extremely helpful and friendly as well. As one brief example, we had a very breezy conversation with Melissa about some of things we planned to see while in Rome, and (without prompting from us) she prepared for us a customized itinerary including tips on when to use cabs/metro and when not, when to use audio-guides and when not, when to pay extra for a guided tour and when not, etc, etc. We were always very happy when we followed the advice she had given us, and we realized later that we should have followed her advice those times we had ignored it.
- Everything in our room was always kept extremely clean.
- As previously mentioned, the location can not be beat (particularly for the money). I met a woman who had been thrilled at the rate she had found at a place near the Spanish Steps. I resisted the temptation to tell her that the Nicolas Inn had cost us 15 euros less per night. Frankly, I have misgivings about posting this review to TripAdvisor because I do not want to give away the secret little place I have found. I am afraid the owners will start getting so busy that they will raise the prices. However, after the level of service we received from them, it would be unjust for me to not write this review.
Home away from home
I have now stayed at the Nicolas Inn twice, three times if you count the fact that my last stay was interrupted by a week-long sojourn in Sicily. Fran�ois and Melissa have pampered me like a favorite uncle. They have given helpful sightseeing hints and have provided me with every comfort. Much as I would like to think they accord me special treatment, I have observed that they accord just as much friendly attention to every guest.
The location is ideal, within walking distance of the main train station and only a few blocks from the Colosseum and the Vittoriano. There are metro and bus stops nearby, and several good eateries.
Home Away From Home!
My wife and I visited Rome with our University daughter and stayed at the Nicolas Inn for five nights. None of us had been to Rome, and we were a bit apprehensive. Everything in the other positive reviews is totally true. We had read them prior to our visit. Nicolas Inn was the greatest. The rooms are on the small side, but very adequate. We stayed in the Inn over New Year's 2004. No problem with noise-- of course we were out in the streets till after midnight, but no problem any night with noise.
The Inn is a short walk from the Metro, just around the corner from the Coloseum and Forum, and gave us an experience of "real life in Rome.". The Inn is clean, beds are great, bathroom is excellent, and the breakfast was served to us in our room every morning! Melissa gave us advice via e-mail prior to our arrival, reserved tickets after we arrived, gave us tips to beat the crowds, tidied our room while we were out, and gave us her cell phone number in case we ran into trouble during the day.
After visiting Florence and Venice, we returned to the Inn for our last night before flying out. Francois stayed late to let us in and greet us. He called one of his taxi driver friends and arranged a 5:15AM pickup for our trip to the airport. And Francois got us a reduced fee for the trip.
We absolutely loved the Inn, and it felt like a home away from home with the hosts' warm support and hospitality. Location, quality accommodations, and personalized support are an unbeatable package at the Nicolas Inn. All three of us were totally happy with the Inn.
Wonderful Stay
Accomodations were great, very clean, very comfortable. Loved teh location - a few blocks from the Roman Forum etc. Hosts were very helpful, booked reservations for us and provided excellent advice on restaurants. Even had breakfast in our room the night before ealry departures. Will stay there again when we return.
Really nice time!!!
This place was a great place to stay..
We got served breakfast in bed!!!...
The location was excellent too...
Francois & Melissa were so helpful with recommendations also..
Fantastic stay in Rome!
The Nicholas Inn made our trip in Rome completely stress-free. Quiet, low-key, and detail-oriented, it is an enchanting oasis that serves as a treat both at the begining and end of a long day in this exhausting city. Melissa and Francois really know how to make their guests feel welcome and at home. We will definitely return in the future.
A must stay if in Rome
Great place. Great people. Great location. Wouldn't chage a thing!
Nicolas Inn is home away from home!!!
It's the hosts that make this place so great. When we arrived they went over a map with us and pointed out the main stuff to see, how to get there, the best days to go, opening hours. Their restaurant recommendations are great. There are several good places to eat right by the B&B but they also suggested places throughout the city.
There were some strikes and protest marches during our stay but again, the hosts told us about them ahead of time so we weren't really inconvenienced.
We had a bit of rain. They offered us umbrella one morning but we said no, thinking the gray sky would turn into sunshine. Well, 5 blocks from returning we were caught in a nasty downpour! We walked in the door drenched to our undies. They immediately gave us extra towels and even made us tea! They just made our time in Rome very relaxing.
We were really happy with the location. The only time we took a bus was to the Vatican (but we walked back, seeing other things along the way) and the Catacombs, which are out of center. There are ruins all of the place by this B&B! And at night it is really pretty when everything is all lit up.
Perfect Location!
We spent two nights early Oct. 2004 - Great location walking distance to all the major cites. The room was quite, newly refurnished, clean with modern bathroom! The bed was very comfortable. we paid 120E which included a nice pastery basket, fruit & yorgurt, Melissa made great coffee and even gave second!!! What a nice treat. Melissa also made us museum reservations - she was extremely helpful.
We definitley recommend this B & B and would stay their again!!
Loved the Nicolas Inn in Rome
We spent 3 lovely nights at the Nicolas Inn in Rome this September. It is a small B & B with very nice rooms, great bathrooms, a perfect location and friendly and helpful owners. Located at 295 Via Cavour close to the forum and the coliseum, it is perfectly located to be in walking distance of sights, restaurants and transportation. It is also next to a wonderful small Italian market. The hostess, Melissa, is American and extremely nice and helpful. If you want a nice place to stay at a reasonable price, you can't do better than this B & B. Here is the contact information: Via Cavour, 295; Scala A, Int. 1;Roma, Italia 00184
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TripAdvisor Reviews Nicolas Inn Rome
Travel Blogs from Rome
When in Rome.....
When in Rome.....
We landed in Civitavecchia yesterday, we have already walked 20 miles. Every time you turn a corner you get WOW'd by another beautiful street or building. However, back to the beginning. We were all packed like good little cruisers the night before. We took an early debarkation cause I thought there would be customs to …
Day 6 of Cruise at sea
Started the day with 2 laps of the running track and half an hour of weights in the gym. The dining room was deserted when we took breakfast at 0815. After breakfast we settled down on deck chairs beside the pool, soaking in the warm, but not baking sun. This is catch up day so I will use it to record my impressions of the cruise. The cabin - excellent. This is one of the new ones created when the ship was refurbished recently. The design ...
Going up
... today, so I missed out on Bramante's Tempietto, and we'll have to go back, which is fine by Xander, because he's keen to see the noon cannon fire from the hillside.
We walked around to the Mausoleo Ossario Garibaldino, a tomb for and monument to Garibaldi's revolutionaries, who fought the French (representing the pope, who opposed Italian unification because it meant he would lose power over Rome, where he was effectively the king) ...
11,000 Beasts, 10,000 Gladiators, 100 Days
... we couldn't wear shorts or tank tops (the basilicas are really strict about modesty in Italy) so I settled for my dress and black tights and I used my scarf as a shall when we went into the duomos. The first one was so plain on the outside, but when we went in, it practically took your breath away, it so ornately decorated. It had a hole in the wall where the light would shine in and focus on a certain spot on a bronze line on ...
Italy, Hurricane Festival & back to Berlin
... we had to take our bags down which was a very
difficult task when you wake up drunk. Once we got down to reception
they informed us we could just stay in the same tents so we had to lug
everything back up the stairs. We stopped at the supermarket and bought
bread, cheese, salad and mayo to make sandwhiches and I thought it would
be a good idea to buy mint vodka to have with. And it was actually
pretty delicious but we didn't end up drinking it till later. Kaidi, ...