The quadratus lumborum block (QLB) is a relatively new regional analgesic technique that could provide analgesia to the abdominal wall and reduce postoperative opioid consumption. We investigated the ...opioid-sparing effect of a unilateral lateral QLB in laparoscopic nephrectomy.
A total of 60 patients undergoing laparoscopic nephrectomy were included in the study. Patients were randomized into two groups as QLB and control group. QLB group received QLB with 25mL 0.25% ropivacaine, and the control group received 25mL 0.9% saline at anterolateral border of quadratus lumborum muscle preoperatively. Opioid consumption and the pain intensity at rest and on movement were measured at 2nd, 6th, 24th, and 48th hour postoperatively. We also assessed the time to first flatus to measure the extent of paralytic ileus and the quality of recovery-15 (QoR-15) questionnaire.
Postoperative opioid consumption was significantly lower in the QLB group than in the control group at 6, 24, and 48h after surgery (
< 0.05). The pain intensity at rest and on movement was significantly lower in the QLB group than in the control group during the first 24 hours after surgery (
< 0.05). The incidence of postoperative nausea and vomiting, time to first flatus, and QoR-15 score did not show significant differences.
Preoperative unilateral QLB successfully decreased postoperative pain and opioid consumption after laparoscopic nephrectomy and could be an option for analgesia after laparoscopic nephrectomy.
The use of mode-dependent transforms for coding directional intra prediction residuals has been previously shown to provide coding gains, but the transform matrices have to be derived from training. ...In this paper, we derive a set of separable mode-dependent transforms by using a simple separable, directional, and anisotropic image correlation model. Our analysis shows that only one additional transform, the odd type-3 discrete sine transform (ODST-3), is required for the optimal implementation of mode-dependent transforms. In addition, the four-point ODST-3 also has a structure that can be exploited to reduce the operation count of the transform operation. Experimental results show that in terms of coding efficiency, our proposed approach matches or improves upon the performance of a mode-dependent transforms approach that uses transform matrices obtained through training.
The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, α- and β-MSH, the majority of attention has focused ...on α-MSH, partly reflecting the absence of β-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding β-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type β-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for β-MSH in the control of human energy homeostasis.
We previously showed that lysophosphatidic acid (LPA) and an adenylyl cyclase inhibitor (ACI) stimulate mitogenic activation of senescent human diploid fibroblasts. Because the modulation of cell ...proliferation may affect wound healing in aged organisms, we studied the effects of LPA and ACI on in vivo skin wound healing in aged Fisher 344 rats. We found that, in aged rats, wound healing improved in animals treated with LPA and/or ACI (relative to untreated controls), as assessed by histological analysis of reepithelialization and immunostaining for proliferating cell nuclear antigen. The age-dependent activation of mitogenic responses by LPA and ACI was confirmed in other cell types. Taken together, our findings suggest that the activation of mitogenic potential in senescent cells by LPA and/or ACI may translate into enhanced in vivo wound healing and tissue regeneration in aged animals.
It is challenging to remove dental implants once they have been inserted into the bone because it is hard to visualize the actual process of bone formation after implant installation, not to mention ...the cellular events that occur therein. During bone formation, contact osteogenesis occurs on roughened implant surfaces, while distance osteogenesis occurs on smooth implant surfaces. In the literature, there have been many in vitro model studies of bone formation on simulated dental implants using flattened titanium (Ti) discs; however, the purpose of this study was to identify the in vivo cell responses to the implant surfaces on actual, three-dimensional (3D) dental Ti implants and the surrounding bone in contact with such implants at the electron microscopic level using two different types of implant surfaces. In particular, the different parts of the implant structures were scrutinized. In this study, dental implants were installed in rabbit tibiae. The implants and bone were removed on day 10 and, subsequently, assessed using scanning electron microscopy (SEM), immunofluorescence microscopy (IF), transmission electron microscopy (TEM), focused ion-beam (FIB) system with Cs-corrected TEM (Cs-STEM), and confocal laser scanning microscopy (CLSM)-which were used to determine the implant surface characteristics and to identify the cells according to the different structural parts of the turned and roughened implants. The cell attachment pattern was revealed according to the different structural components of each implant surface and bone. Different cell responses to the implant surfaces and the surrounding bone were attained at an electron microscopic level in an in vivo model. These results shed light on cell behavioral patterns that occur during bone regeneration and could be a guide in the use of electron microscopy for 3D dental implants in an in vivo model.
New 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives (1 and 2) were synthesized as an “off−on” fluorescent chemosensor and fluorescent chemodosimeter for Cu2+ and Pb2+. Compound 1 ...displayed selective and large chelation enhanced fluorescence effects with Pb2+ and Cu2+ among the metal ions examined. On the other hand, compound 2, a fluorescent chemodosimeter, effectively recognized Cu2+ via a selective hydrolysis of the acetyl group.
Studies of the Peptide YY and Neuropeptide Y2 Receptor Genes in Relation to Human Obesity and Obesity-Related Traits
Chiao-Chien Connie Hung 1 ,
Fraser Pirie 2 ,
Jian’an Luan 3 ,
Emma Lank 1 ,
Ayesha ...Motala 2 ,
Giles S.H. Yeo 1 ,
Julia M. Keogh 1 ,
Nicholas J. Wareham 3 ,
Stephen O’Rahilly 1 and
I. Sadaf Farooqi 1
1 University Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, U.K
2 Endocrine/Diabetes Unit, Nelson R. Mandela School of Medicine, University of Natal, Natal, South Africa
3 Department of Public Health and Epidemiology, Addenbrookes’ Hospital, Cambridge, U.K
Address correspondence and reprint requests to Stephen O’Rahilly or I. Sadaf Farooqi, University Department of Clinical Biochemistry,
Addenbrookes’ Hospital, Cambridge, CB2 2QQ, U.K. E-mail: sorahill{at}hgmp.mrc.ac.uk or ifarooqi{at}hgmp.mrc.ac.uk
Address correspondence and reprint requests to Stephen O’Rahilly or I. Sadaf Farooqi, University Department of Clinical Biochemistry,
Addenbrookes’ Hospital, Cambridge, CB2 2QQ, U.K. E-mail: sorahill{at}hgmp.mrc.ac.uk or ifarooqi{at}hgmp.mrc.ac.uk
Abstract
Peptide-YY (PYY) is secreted from endocrine L-cells of the gastrointestinal tract in response to caloric ingestion and may
mediate postprandial satiety through the hypothalamic neuropeptide Y2 receptor (Y2R). We examined whether variants in the
genes encoding PYY and Y2R might be associated with obesity-related phenotypes in humans. Among 101 subjects with severe early-onset
obesity and a history of hyperphagia, we found two rare sequence variants—L73P and IVS2 + 32delG—in PYY and three rare missense mutations—L40F, F87I, and A172T—in Y2R . Although none of these were found in 100 normal-weight white control subjects, L73P in PYY and F87I and A172T in Y2R did not segregate with obesity in family studies, and family data were unavailable for IVS2 + 32delG in PYY and L40F in Y2R . Two common single nucleotide polymorphisms (SNPs), R72T and IVS3 + 68C>T, in PYY were in tight linkage disequilibrium but showed no association with BMI in a large white population. In the Y2R , two SNPs, 585T>C and 936T>C, were found and were in tight linkage disequilibrium. Men, homozygous for the rarer variant,
had significantly lower BMI ( P = 0.017), waist-to-hip ratio ( P = 0.013), and, surprisingly, higher nonesterified fatty acid levels ( P = 0.01). In conclusion, mutations in PYY and Y2R are not commonly found in humans with severe early-onset obesity. The relationship between common variants in Y2R and obesity-related traits deserves further exploration in other populations.
GOOS, Genetics of Obesity Study
MS-PCR, mutagenically separated PCR
NEFA, nonesterified fatty acid
NPY, neuropeptide Y
RFLP, restriction fragment–length polymorphism
POMC, proopiomelanocortin
PYY, peptide-YY
SNP, single nucleotide polymorphism
Y2R, Y2 receptor
Footnotes
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org .
Accepted June 9, 2004.
Received April 30, 2004.
DIABETES
Background Vascular endothelial growth factor (VEGF) is a crucial proangiogenic component in pancreatic ductal adenocarcinoma (PDA), and its high expression levels have been correlated with poor ...prognosis and early postoperative recurrence. Angiotensin II (AngII), which has been shown to increase VEGF production in a variety of cancers, is actively generated in the pancreas. We hypothesized that AngII plays a crucial role in PDA-associated angiogenesis. Study Design We analyzed the expression and localization of AngI converting enzyme (ACE) and AngII type 1 receptor (AT1R) in relation to VEGF in matched invasive human PDA (n = 25) and surrounding nonmalignant tissues using real-time polymerase chain reaction, Western immunoblotting, and immunohistochemistry. VEGF levels in conditioned media of HS766T and PK9 PDA cells treated with or without AngII (10−7 mol/L) were measured by ELISA. The effects of an AT1R blocker (losartan) and an ACE inhibitor (captopril) on VEGF production and cellular proliferation were also examined. Results ACE and AT1R mRNA and protein levels were significantly upregulated in 19 of the 25 neoplastic tissues examined (∼75%), when compared with matching controls. VEGF expression was significantly higher in tissues that expressed high levels of AT1R and ACE (n = 19), compared with low levels (n = 4) or negative (n = 2) cases. ACE protein collocalized with AT1R and VEGF in the malignant ducts and in the stromal cells. Addition of AngII significantly enhanced VEGF mRNA production and protein secretion, an effect that was prevented when cells were preincubated with captopril or losartan. Blocking endogenous AngII by captopril or losartan significantly suppressed cell proliferation. Conclusions Both ACE and AT1R are functionally expressed in PDA and may be involved in tumor angiogenesis. Because AT1R blockers and ACE inhibitors are already widely used clinically, they may represent a potential novel and promising strategy for controlling angiogenesis, prevention of metastasis, and prolongation of survival in patients with primary or metastatic PDA.
Dependence of the spectral functions near the Fermi level on temperature and rare-earth atom doping was studied in detail for strongly correlated alloys Sm1−xEuxB6 and Yb1−xLuxB12 by photoelectron ...spectroscopy at ∼8000 eV as well as at 7 and 8.4 eV. It was found that the 4f lattice coherence and intrinsic gap are robust for Sm1−xEuxB6 at least up to the Eu substitution of x = 0.15 while both collapse by Lu substitution already at x = 0.125 for Yb1−xLuxB12. As for the temperature dependence of the spectral shapes near the Fermi level at low temperatures, rather contrasting results were observed between YbB12 and SmB6. Although the gap shape does not change below 15 K for YbB12 with the characteristic temperature T* of 80 K, the spectral shape of SmB6 with a T* of 140 K shows that the peak beyond the gap is further increased below 15 K. The temperature dependence of the spectra near the intrinsic gap is clearly different between SmB6 and YbB12, although both materials have so far been categorized in the same kind of strongly correlated semiconductor. The possibility of the surface contribution is discussed for SmB6.
Abstract
Background
There is a high prevalence of subclinical cardiac dysfunction in people with type 2 diabetes (T2D) which is associated with subsequent development of heart failure. Dysregulated ...myocardial calcium handling has been demonstrated in animal models of T2D and may be a key mechanism driving the development of heart failure. Manganese-enhanced cardiac magnetic resonance imaging (MEMRI) provides a unique method to assess in vivo myocardial calcium handling.
Purpose
To determine whether myocardial calcium handling is perturbed in people with T2D with no history of cardiovascular disease. We hypothesised that myocardial manganese uptake would be reduced in people with T2D compared with healthy volunteers.
Methods
Cross-sectional case-control study, adults with (n=20) and without (n=9) T2D underwent both gadolinium-enhanced MRI and MEMRI. Standard gadolinium-enhanced MRI was used to assess cardiac structure, function and tissue characteristics. MEMRI scans were performed within two weeks of the initial scan. Native T1 maps were obtained in the mid-short axis slice position using a Modified Look-Locker Inversion recovery sequence. An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg (0.1 mL/kg) at 1 mL/min) was administered and T1 maps at the same location were repetitively acquired every 2.5 min for 30 min. Regions of interest were drawn in the inferoseptal segment and blood pool for all T1 maps from 0 to 30 min by a single observer. The primary outcome was the rate of manganese uptake which was assessed by Patlak modelling as a measure of myocardial calcium handling. Manganese uptake constants were compared using analysis of co-variance, with age, sex and body mass index as co-variates.
Results
Subjects with T2D were older (62±7 vs. 57±5 years, p=0.046) but body mass index (29.0±4.5 vs. 26.2±3.4 kg/m2, p=0.106), systolic (135±16 vs. 134±17 mmHg, p=0.809) and diastolic (81±10 vs. 83±9 mmHg, p=0.736) blood pressures were similar. Compared to control subjects, participants with T2D had normal systolic function but more concentric left ventricular remodelling (mass/volume ratio 0.90±0.14 vs. 0.71±0.06 g/mL, p<0.001) and reduced peak early diastolic strain rate (0.64±0.17 vs. 0.91±0.26 s–1, p=0.002). Myocardial manganese uptake was substantially reduced in people with T2D compared with controls (6.51±1.46 vs. 8.45±2.52 ml/100 g of tissue/min, p=0.003) (Figure 1).
Conclusions
For the first time, we have demonstrated in vivo that despite no history of cardiovascular disease and normal systolic function, patients with T2D have marked impairment of myocardial calcium handling. This has potential major implications for the pathogenesis, diagnosis and treatment of diabetic cardiomyopathy.
Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and National Institute for Health Research
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