Gautham Chitragari

Consequences of hypogastric artery ligation, embolization, or coverage.

OBJECTIVE Interruption of the hypogastric artery by ligation, embolization, or coverage frequently results in ischemic complications. The aim of this study was to compare the rate and risk factors for the development of ischemic complications after interruption of the hypogastric artery in obstetrics and gynecology (OBG), vascular surgery, oncology, and trauma patients. METHODS MEDLINE, Ovid, and Scopus were searched for articles containing data of patients who underwent interruption of the hypogastric artery. Based on the indication, details of the procedure, and complications developed, data were categorized and a systematic review was done to evaluate any significant differences. RESULTS A total of 394 patients (median age, 48.5 years) from 124 papers were included in the study; 31% of the study population was male and 69% was female. Indication for interruption was OBG related in 53.3%, vascular surgery related in 25.1%, oncology related in 17.5%, and trauma related in 4.1% of patients. Overall ischemic complication rate was 22.6%, comprising buttock claudication in 12.2%, buttock necrosis in 4.8%, erectile dysfunction in 2.7%, spinal cord ischemia in 4.0%, colonic ischemia in 2.5%, and bladder necrosis in 0.8%. Complications were fewer in patients younger than the median age of 48.5 years (12.8%) compared with those older than the median age (36.3%; P < .01), women compared with men (13.1% vs 41.7%; P < .01), OBG patients compared with vascular surgery patients (9.5% vs 37.4%; P < .01), patients after ligation compared with embolization (9.4% vs 31.0%; P < .01), and proximal interruption compared with distal interruption (19.6% vs 51.4%; P < .01). No significant difference in complications was seen after bilateral interruption compared with unilateral interruption (20.6% vs 27.1%; P > .05). Similarly, no significant difference in complication rate was seen with the type of embolization material used. Among OBG patients, ligations resulted in fewer complications compared with embolization (4.1% vs 16.7%; P < .01). Among vascular surgery patients, bilateral embolization resulted in a higher rate of complications compared with bilateral ligation (83.3% vs 30.5%; P < .01). Among oncology patients, fewer complications were seen after proximal interruption compared with distal interruption (25.5% vs 75%; P = .01). No significant differences in outcome were seen with regard to gender, laterality, and material used for embolization when patients were compared within each specialty. CONCLUSIONS Interruption of the hypogastric artery is relatively safe in young and OBG patients compared with vascular surgery and oncology patients. Ligation of the hypogastric arteries is preferred to embolization, and proximal embolization should be preferred to distal embolization to decrease the risk of ischemic complications. Randomized controlled trials with larger sample size are needed to definitively elucidate clear risk factors for development of complications after hypogastric artery interruption.

Prosthetic Options Available for the Diabetic Lower Limb Amputee

Although the rate of lower limb amputation in patients with diabetes is decreasing, amputation still remains a major complication of diabetes. Prosthetics have been long used to help amputees ambulate. The last decade has seen many advances in prostheses with the enhanced understanding of the mechanics of ambulation and improved use of technology. This review describes the different types of prosthetic options available for below knee, ankle, and foot amputees, emphasizing the latest advances in prosthetic design.

Effect of Pulsatile and Continuous Flow on Yes-Associated Protein

Yes-associated protein (YAP) is a mechanosignaling protein that relays mechanical information to the nucleus by changing its level of phosphorylation. We hypothesize that different flow patterns show differential effect on phosphorylated YAP (pYAP) (S127) and total YAP and could be responsible for flow dependent localization of atherosclerosis. Confluent human umbilical vein endothelial cells (HUVECs) seeded on fibronectin-coated glass slides were exposed to continuous forward flow (CFF) and pulsatile forward flow (PFF) using a parallel plate flow chamber system for 30 minutes. Cell lysates were prepared and immunoblotted to detect the levels of phosphorylated YAP and total YAP. HUVECs exposed to both PFF and CFF showed a mild decrease in the levels of both pYAP (S127) and total YAP. While the levels of pYAP (S127) decreased to 87.85 and 85.21% of static control with PFF and CFF, respectively, the levels of total YAP significantly decreased to 91.31 and 92.27% of static control. No significant difference was seen between CFF and PFF on their effect on pYAP (S127), but both conditions resulted in a significant decrease in total YAP at 30 minutes. The results of this experiment show that the possible effect of different types of flow on YAP is not induced before 30 minutes. Experiments exposing endothelial cells to various types of flow for longer duration of time could help to elucidate the role of YAP in the pathogenesis of atherosclerosis.

Indian Spices for the Management of Diabetic Foot Complications

Despite significant advances in medicine and surgery, the prevalence of diabetic foot complications still remains high in both developed and developing countries of the world. Curcumin, the active component of turmeric, an Indian spice has been extensively studied and is known to possess many biological activities including wound healing. The current review describes the available evidence on the utility of curcumin in treating diabetic foot ulcers.

Shear Stress Induces Change in Extracellular Signal-Regulated Kinase 5 Levels with Sustained Activation under Disturbed and Continuous Laminar Flow

&NA; Extracellular signal‐regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum‐starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to‐and‐fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber. At the end of experimentation, cell lysates were immunoblotted with antibodies to phospho‐ERK5 and total ERK5. ERK5 activation was assessed by the levels of phosphorylated ERK5. The densitometric mean ± SEM is calculated and analyzed by ANOVA. p < 0.05 is considered significant. Levels of ERK5 decreased with all flow conditions with the largest decrease in TFF flow condition. TFF and CLF exhibited sustained ERK5 phosphorylation in HUVECs stimulated for up to 4 hours. PFF had transient phosphorylation of ERK5 at 2 hours, which then became undetectable at 4 hours of exposure to flow. Also, TFF and CLF both showed decreased levels at 4 hours, suggesting a decrease in activation for these flow conditions. Exposure of HUVEC to different types of shear stress results in varying patterns of activation of ERK5. Activation of ERK5 with TFF suggests a role in the pathogenesis of atherosclerosis and vascular remodeling under disturbed flow conditions.

African Trypanosome-Induced Blood-Brain Barrier Dysfunction under Shear Stress May Not Require ERK Activation.

African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.

Characterization of extracellular signal-regulated kinase 5 levels in human umbilical vein endothelial cells exposed to disturbed and uniform flow.

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial cell integrity and protect from vascular dysfunction under continuous laminar flow. However, the effect of flow on ERK5 levels has not been determined. Confluent human umbilical vein endothelial cells (HUVECs) were seeded on fibronectin coated glass slides and serum starved for 2 hours with 1% fetal bovine serum (FBS). HUVECs were then exposed to to and fro flow (TFF), pulsatile forward flow (PFF), or continuous laminar flow (CLF) in a parallel plate flow chamber for up to 2 hours. At the end of experiment, cell lysates were prepared and immunoblotted with antibodies to total ERK5. Both CLF and TFF exhibited a decrease in ERK5 after levels after 2-hour exposure. However, the level of ERK5 for PFF remained the same. Disturbed, but not uniform pulsatile, flow decreases ERK5 levels in HUVECs.