121 research outputs found
Intravascular Stapler for âOpenâ Aortic Surgery: Preliminary Results
NumeraciĂłn errĂłnea en el original
Robot-assisted laparoscopic surgery of the infrarenal aorta: The early learning curve
Background Recently introduced robot-assisted laparoscopic surgery (RALS) facilitates endoscopic surgical manipulation and thereby reduces
the learning curve for (advanced) laparoscopic surgery. We present our learning curve with RALS for aortobifemoral bypass
grafting as a treatment for aortoiliac occlusive disease.
Methods Between February 2002 and May 2005, 17 patients were treated in our institution with robot-assisted laparoscopic aorto-bifemoral
bypasses. Dissection was performed laparoscopically and the robot was used to make the aortic anastomosis. Operative time,
clamping time, and anastomosis time, as well as blood loss and hospital stay, were used as parameters to evaluate the results
and to compare the first eight (group 1) and the last nine patients (group2).
Results Total median operative, clamping, and anastomosis times were 365 min (range: 225â589 min), 86 min (range: 25â205 min), and
41 min (range: 22â110 min), respectively. Total median blood loss was 1,000 ml (range: 100â5,800 ml). Median hospital stay
was 4 days (range: 3â57 days). In this series 16/18 anastomoses were completed with the use of the robotic system. Three patients
were converted (two in group 1, one in group 2), and one patient died postoperatively (group 1). Median clamping and anastomosis
times were significantly different between groups 1 and 2 (111 min [range: 85â205 min] versus 57.5 min [range: 25â130 min],
p < 0.01 and 74 min [range: 40â110 min] versus 36 min [range: 22â69 min], p < 0.01, respectively) Total operative time, blood loss, and hospital stay showed no significant difference between groups
1 and 2.
Conclusions Robot-assisted aortic anastomosis was shown to have a steep learning curve with considerable reduction of clamping and anastomosis
times. However, due to a longer learning curve for laparoscopic dissection of the abdominal aorta, operation times were not
significantly shortened. Even with robotic assistance, laparoscopic aortoiliac surgery remains a complex procedure
Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling
PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling. © 2023 The Author(s
CD34+/M-cadherin+ Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoEâ/â Mice
BACKGROUND: Cell-based therapy shows promise in treating peripheral arterial disease (PAD); however, the optimal cell type and long-term efficacy are unknown. In this study, we identified a novel subpopulation of adult progenitor cells positive for CD34 and M-cadherin (CD34âș/M-cadâș BMCs) in mouse and human bone marrow. We also examined the long-lasting therapeutic efficacy of mouse CD34âș/M-cadâș BMCs in restoring blood flow and promoting vascularization in an atherosclerotic mouse model of PAD. METHODS AND FINDINGS: Colony-forming cell assays and flow cytometry analysis showed that CD34âș/M-cadâș BMCs have hematopoietic progenitor properties. When delivered intra-arterially into the ischemic hindlimbs of ApoEâ»/â» mice, CD34âș/M-cadâș BMCs alleviated ischemia and significantly improved blood flow compared with CD34âș/M-cadâ» BMCs, CD34â»/M-cadâș BMCs, or unselected BMCs. Significantly more arterioles were seen in CD34âș/M-cadâș cell-treated limbs than in any other treatment group 60 days after cell therapy. Furthermore, histologic assessment and morphometric analyses of hindlimbs treated with GFPâș CD34âș/M-cadâș cells showed that injected cells incorporated into solid tissue structures at 21 days. Confocal microscopic examination of GFPâș CD34âș/M-cadâș cell-treated ischemic legs followed by immunostaining indicated the vascular differentiation of CD34âș/M-cadâș progenitor cells. A cytokine antibody array revealed that CD34âș/M-cadâș cell-conditioned medium contained higher levels of cytokines in a unique pattern, including bFGF, CRG-2, EGF, Flt-3 ligand, IGF-1, SDF-1, and VEGFR-3, than did CD34âș/M-cadâ» cell-conditioned medium. The proangiogenic cytokines secreted by CD34âș/M-cadâș cells induced oxygen- and nutrient-depleted endothelial cell sprouting significantly better than CD34âș/M-cadâ» cells during hypoxia. CONCLUSION: CD34âș/M-cadâș BMCs represent a new progenitor cell type that effectively alleviates hindlimb ischemia in ApoEâ»/â» mice by consistently improving blood flow and promoting arteriogenesis. Additionally, CD34âș/M-cadâș BMCs contribute to microvascular remodeling by differentiating into vascular cells and releasing proangiogenic cytokines and growth factors
Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction
Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853(â)]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage
Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in EnvironmentâSources, Risks, Biodegradation
Recently, the increased use of monocyclic
non-steroidal anti-inflammatory drugs has resulted in
their presence in the environment. This may have
potential negative effects on living organisms. The
biotransformation mechanisms of monocyclic nonsteroidal
anti-inflammatory drugs in the human body
and in other mammals occur by hydroxylation and
conjugation with glycine or glucuronic acid.
Biotransformation/biodegradation of monocyclic
non-steroidal anti-inflammatory drugs in the environment
may be caused by fungal or bacterial microorganisms.
Salicylic acid derivatives are degraded by
catechol or gentisate as intermediates which are
cleaved by dioxygenases. The key intermediate of
the paracetamol degradation pathways is hydroquinone.
Sometimes, after hydrolysis of this drug, 4-
aminophenol is formed, which is a dead-end metabolite.
Ibuprofen is metabolized by hydroxylation or
activation with CoA, resulting in the formation of
isobutylocatechol. The aim of this work is to attempt
to summarize the knowledge about environmental risk
connected with the presence of over-the-counter antiinflammatory
drugs, their sources and the biotransformation
and/or biodegradation pathways of these
drugs
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