Publications by authors named "Ankur Gandhi"

13 Publications

  • Page 1 of 1

Biological characterization of dehydrated amniotic membrane allograft: Mechanisms of action and implications for wound care.

J Biomed Mater Res B Appl Biomater 2020 11 26;108(8):3076-3083. Epub 2020 May 26.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.

There is a growing clinical demand in the wound care market to treat chronic wounds such as diabetic foot ulcers. Advanced cell and tissue-based products (CTPs) are often used to address challenging chronic wounds where healing has stalled. These products contain active biologics such as growth factors and cytokines as well as structural components that support and stimulate cell growth and assist in tissue regeneration. This study addresses the in vitro biologic effects of a clinically available dehydrated amniotic membrane allograft (DAMA). The broad mechanism of action results from DAMA's biologic composition that leads to stimulation of cell migration cell proliferation, and reduction of pro-inflammatory cytokines. Results show that DAMA possesses growth factors and cytokines such as EGF, FGF, PDGFs, VEGF, TGF-β, IL-8, and TIMPs 1 and 2. Furthermore, in vitro experiments demonstrate that DAMA stimulates cell proliferation, cell migration, secretion of collagen type I, and the reduction of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. This study findings are consistent with the clinical benefits previously published for DAMA and other CTPs in chronic wounds suggesting that the introduction of DAMA to non-healing, complex wounds helps to improve the wound milieu by providing essential structural components, cytokines, and growth factors to create an appropriate environment for wound healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm.b.34635DOI Listing
November 2020

Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of new 2-(4-isobutylphenyl)propanoic acid derivatives.

J Enzyme Inhib Med Chem 2012 Feb 25;27(1):110-6. Epub 2011 May 25.

Department of Pharmaceutical Chemistry, Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences(ARIBAS) , New Vallabh Vidyanagar, Gujarat, India.

Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl)propanoic acid derivatives containing 1,3,4-thiadiazole and thiadiazolo[3,2-a][1,3,5]triazine-5-thione nucleus is reported here. The structures of new compounds are supported by IR, (1)H & (13)C NMR data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA). Compound 4i and 5f showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid-induced writhings and 0.7 and 0.65 of severity index, respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/14756366.2011.578743DOI Listing
February 2012

The effects of low-intensity pulsed ultrasound upon diabetic fracture healing.

J Orthop Res 2011 Feb 30;29(2):181-8. Epub 2010 Sep 30.

Department of Orthopaedics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103, USA.

In the United States, over 17 million people are diagnosed with type 1 diabetes mellitus (DM) with its inherent morbidity of delayed bone healing and nonunion. Recent studies demonstrate the utility of pulsed low-intensity ultrasound (LIPUS) to facilitate fracture healing. The current study evaluated the effects of daily application of LIPUS on mid-diaphyseal femoral fracture growth factor expression, cartilage formation, and neovascularization in DM and non-DM BB Wistar rats. Polymerase chain reaction (PCR) and ELISA assays were used to measure and quantify growth factor expression. Histomorphometry assessed cartilage formation while immunohistochemical staining for PECAM evaluated neovascularization at the fracture site. In accordance with previous studies, LIPUS was shown to increase growth factor expression and cartilage formation. Our study also demonstrated an increase in fracture callus neovascularization with the addition of LIPUS. The DM group showed impaired growth factor expression, cartilage formation, and neovascularization. However, the addition of LIPUS significantly increased all parameters so that the DM group resembled that of the non-DM group. These findings suggest a potential role of LIPUS as an adjunct for DM fracture treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.21223DOI Listing
February 2011

The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix.

Anesth Analg 2010 Jul 3;111(1):221-9. Epub 2010 Jun 3.

Brigham and Women's Hospital, MRB-611, 75 Francis St., Boston, MA 02115-6110, USA.

Background: Nerve blocks of long duration are often desirable in perioperative and postoperative situations. The relationship between the duration of such blocks and the rate at which a local anesthetic is released is important to know for developing a localized drug delivery system that will optimize block duration.

Methods: Lidocaine concentration was varied in 1 series of formulations (OSB-L) containing a constant amount of release rate modifier. In another series (OST-R), the release rate modifier was varied while the lidocaine content was held constant. Release kinetics were measured in vitro and correlated to the in vivo duration of antinociceptive and motor block effects when the formulation was implanted next to the rat sciatic nerve. In parallel studies, rats receiving different formulations of slow-release lidocaine were fixed by intracardiac perfusion with 4% paraformaldehyde and nerve-muscle tissue taken for histopathological analysis.

Results: In this study, we have demonstrated that the most important variable for effecting functional nerve block, i.e., the blockade of impulses in the relevant fibers of the sciatic nerve, is the rate of lidocaine release at that time. For the OSB-L formulations (lidocaine concentrations of 1.875%, 3.75%, 7.5%, and 15% at a constant release rate modifier of 5%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 0.91 +/- 0.28 and 1.75 +/- 0.61 mg/h, respectively. For the OST-R formulations (16% lidocaine with release rate modifier concentrations of 1.875%, 3.75%, 7.5%, and 15%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 2.33 +/- 1.39 and 4.34 +/- 1.09 mg/h, respectively. The OSB-L formulations showed a dose-dependent increase in block duration proportional to an increase in initial lidocaine concentration, whereas the OST-R formulations showed a nonmonotonic relationship between release rate modifier concentration and block duration. The histopathological studies at 24 hours, 3, 5, or 7 days, and 4 weeks after the implantation revealed inflammatory reactions with degrees correlated with lidocaine content, but limited to the connective tissue and muscle immediately surrounding the implanted material. Despite these observed inflammatory reactions, nociceptive and motor block function returned to normal, preimplantation values in all animals.

Conclusions: Increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block. However, decreasing the release rate per se does not give a proportional increase in block duration. Instead, there seems to be an optimal, intermediate release rate for achieving the maximum duration of block.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ANE.0b013e3181dd2690DOI Listing
July 2010

An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade.

Anesth Analg 2009 Mar;108(3):1027-33

Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration-approved matrix containing lidocaine that is capable of local delivery for several days.

Methods: Xybrex, an absorbable, controlled-release delivery system containing 16% (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2% = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h.

Results: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 +/- 2.0 h, 6.9 +/- 1.7 h and partial analgesia for 60.0 +/- 5.4 h, 58.8 +/- 4.2 h, respectively, compared to 0.61 +/- 0.03 h of complete analgesia and 0.96 +/- 0.03 h of partial analgesia by sciatic block from the 2% lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 +/- 3.3 h, 17.6 +/- 3.3 h with full recovery in 352.0 +/- 55.7 h (14.7 +/- 2.3 days), 579.0 +/- 36.1 h (24.1 +/- 1.5 days) respectively. Data are reported as mean +/- SE. P < 0.001 for all Xybrex groups compared to the 2% lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2% lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug.

Conclusions: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ane.0b013e318193596aDOI Listing
March 2009

Complications of ankle fracture in patients with diabetes.

J Am Acad Orthop Surg 2008 Mar;16(3):159-70

Department of Orthopaedics, New Jersey Medical School, Newark, NJ, USA.

Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Complications of impaired wound healing, infection, malunion, delayed union, nonunion, and Charcot arthropathy are prevalent in this patient population. Controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation. Patients with diabetes are at significant risk for soft-tissue complications. In addition, diabetic ankle fractures heal, but significant delays in bone healing exist. Also, Charcot ankle arthropathy occurs more commonly in patients who were initially undiagnosed and had a delay in immobilization and in patients treated nonsurgically for displaced ankle fractures. Several techniques have been described to minimize complications associated with diabetic ankle fractures (eg, rigid external fixation, use of Kirschner wires or Steinmann pins to increase rigidity). Regardless of the specifics of treatment, adherence to the basic principles of preoperative planning, meticulous soft-tissue management, and attention to stable, rigid fixation with prolonged, protected immobilization are paramount in minimizing problems and yielding good functional outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5435/00124635-200803000-00007DOI Listing
March 2008

Diabetic fracture healing.

Foot Ankle Clin 2006 Dec;11(4):805-24

Department of Orthopaedics, University of Medicine & Dentistry-New Jersey Medical School, 185 South Orange Avenue, MSB G-574, Newark, NJ 07103, USA.

Patients with diabetic ankle fractures consistently are at greater risk of sustaining a complication during treatment than nondiabetics.other medical comorbidities, especially Charcot neuroarthropathy and peripheral vascular disease, play distinct roles in increasing these complication rates. Many options for nonoperative and operative treatment exist, but respect for soft tissue management and attention to stable, rigid fixation with prolonged immobilization and prolonged restricted weight bearing are paramount in trying to minimize problems and yield functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fcl.2006.06.009DOI Listing
December 2006

Electrical bone stimulation devices in foot and ankle surgery: types of devices, scientific basis, and clinical indications for their use.

Foot Ankle Int 2006 Feb;27(2):148-56

Department of Orthopaedic Surgery, UMDNJ-Newark, New Jersey Medical School, 90 Bergen Street, #7300 DOC, Newark, NJ 07103, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/107110070602700216DOI Listing
February 2006

The effects of local platelet rich plasma delivery on diabetic fracture healing.

Bone 2006 Apr 20;38(4):540-6. Epub 2005 Dec 20.

New Jersey Institute of Technology, Department of Biomedical Engineering, 323 Martin Luther King Jr. Boulevard, Newark, New Jersey 07102, USA.

Several studies have documented that diabetes impairs bone healing clinically and experimentally. The percutaneous delivery of platelet rich plasma (PRP) was used in the diabetic BB Wistar femur fracture model to investigate the use of PRP as a concentrated source of critical early growth factors on bone healing. PRP delivery at the fracture site normalized the early (cellular proliferation and chondrogenesis) parameters while improving the late (mechanical strength) parameters of diabetic fracture healing. These results suggest a role for PRP in mediating diabetic fracture healing and potentially other high risk fractures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2005.10.019DOI Listing
April 2006

The role of platelet-rich plasma in foot and ankle surgery.

Foot Ankle Clin 2005 Dec;10(4):621-37, viii

Department of Orthopaedics, University of Medicine & Dentistry-New Jersey Medical School, 185 South Orange Avenue, MSB G-574, Newark, NJ 07103, USA.

Platelet-rich plasma (PRP), derived from autologous blood, is defined as a volume of plasma that has a platelet concentration that typically is five times greater (approximately 1,000,000/microl) than physiologic levels. PRP serves as a reservoir of critical growth factors, including platelet-derived growth factor, transforming growth factor-beta, and insulin-like growth factor-I. Although there is an abundance of literature pertaining to dental applications, this article highlights the use of PRP in orthopedic applications, ranging from PRP preparation to in vitro and in vivo studies to clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fcl.2005.06.009DOI Listing
December 2005

The effects of local insulin delivery on diabetic fracture healing.

Bone 2005 Oct;37(4):482-90

Department of Orthopaedics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, MSB-G574, Newark, NJ 07103, USA.

Several studies have documented that diabetes impairs bone healing clinically and experimentally. Systemic insulin treatment has been shown to ameliorate impaired diabetic bone healing. However, these studies failed to distinguish between a direct and a systemic effect of insulin upon bone healing. A novel intramedullary insulin delivery system was used in the diabetic BB Wistar femur fracture model to investigate the potential direct effects of insulin on bone healing. Insulin delivery at the fracture site normalized the early (cellular proliferation and chondrogenesis) and late (mineralized tissue, cartilage content and mechanical strength) parameters of diabetic fracture healing without affecting the systemic parameters of blood glucose. These results suggest a critical role for insulin in directly mediating fracture healing and that decreased systemic insulin levels in the diabetic state lead to reduced localized insulin levels at fracture site with concomitant increases in diabetic fracture healing time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2005.04.039DOI Listing
October 2005

Effects of triiodothyronine pretreatment on beta-adrenergic responses in stunned cardiac myocytes.

J Cardiothorac Vasc Anesth 2003 Aug;17(4):486-90

Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA.

Objective: To investigate whether triiodothyronine pretreatment enhanced beta-adrenergic responses in stunned myocardium and whether this acute effect of triiodothyronine was mediated through the cyclic adenosine 3',5'-monophosphate (AMP) system.

Design: A prospective study.

Setting: University laboratory.

Participants: Rabbits.

Interventions: Rabbit ventricular myocytes were isolated and placed in a medium equilibrated with either air (control) or with 95% N(2) and 5% CO(2) (stunned) for 15 minutes at 37 degrees C. The stunned myocytes were reoxygenated with air for 30 minutes. Triiodothyronine (10 nmol/L) and/or isoproterenol (0.1 nmol/L) was added to the myocytes. Myocyte shortening was measured by using a video-edge detector.

Measurements And Main Results: In electrically stimulated cells, the basal values of the percent shortening (22%-30%) and the maximum rate of shortening (22%-25%) were significantly reduced in the stunned myocytes. Isoproterenol (5 minutes) alone significantly increased the percent shortening in the control (from 3.70 +/- 0.36 to 4.14 +/- 0.37) but not in the stunned myocytes (from 2.60 +/- 0.30 to 3.15 +/- 0.27). Triiodothyronine (5 minutes) alone significantly increased the percent shortening in the control (from 3.75 +/- 0.36 to 4.34 +/- 0.45) and in the stunned myocytes (from 2.91 +/- 0.2 to 3.85 +/- 0.26). After triiodothyronine pretreatment for 5 minutes, isoproterenol caused greater increases in the percent shortening in both the control (37%) and the stunned myocytes (62%) than either agent alone. Isoproterenol or triiodothyronine caused small increases in the maximum rate of shortening in the control (14%-16%) and the stunned myocytes (34%-49%). After triiodothyronine pretreatment, isoproterenol caused greater increases in the maximum rate of shortening in both groups (control: 41%, stunned: 73%) than either agent alone. Isoproterenol caused an increase in the level of cyclic AMP (rho;moles/10(5) myocytes) in the control (from 2.92 +/- 0.47 to 3.77 +/- 0.43) but not in the stunned myocytes (from 2.42 +/- 0.25 to 2.42 +/- 0.20). Triiodothyronine pretreatment did not cause any change in cyclic AMP levels in the control (2.50 +/- 0.29) or in the stunned myocytes (2.60 +/- 0.40). After triiodothyronine pretreatment, isoproterenol caused a small increase in the cyclic AMP level in the control but not in the stunned myocytes.

Conclusions: The data showed that the myocardial beta-adrenergic responses were more sensitive to ischemic insult than the triiodothyronine responses. Triiodothyronine pretreatment enhanced beta-adrenergic responses in both the control and the stunned myocytes. However, this acute positive inotropic effect of triiodothyronine might not be mediated through the cyclic AMP system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1053-0770(03)00154-xDOI Listing
August 2003

Negative effect of nitric oxide on shortening-frequency relationship in cardiac myocytes is diminished after simulated ischemia-reperfusion.

Basic Res Cardiol 2003 Sep 19;98(5):311-8. Epub 2003 Jul 19.

Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA.

Increasing stimulation rate increases function in cardiac myocytes and nitric oxide and cyclic GMP inhibit this effect. We tested the hypothesis that myocyte stunning would blunt both the effects of increases in rate and of nitric oxide and cyclic GMP. Ventricular myocytes from 11 rabbits were used to determine maximum rate of shortening (R(max), microm/s) and % shortening during control and after simulated ischemia [15 min 95% N(2)- 5% CO(2)] and reperfusion [reoxygenation]. Measurements were obtained at 1-4 Hz with vehicle, 1H[1,2,4]oxadiazolo[4,3,alpha] quinoxaline-1-one (ODQ) 10(-6) M, soluble guanylyl cyclase inhibitor, or N(G)-nitro-L-arginine methyl ester, nitric oxide synthase inhibitor (L-NAME) 10(-5) M. In control, increases in rate increased R(max) from 69 +/- 3 to 254+/-12 and % shortening from 5.3 +/- 0.3 to 8.7 +/- 0.5. Both ODQ and L-NAME shifted values higher. With stunning, the effects of pacing on Rmax and % shortening were blunted and ODQ and L-NAME failed to alter these values. Cyclic GMP was 322+/-37 pmol/10(5) myocytes at baseline and these values were lowered by ODQ (244 +/- 31) and LNAME (207 +/- 23), and similar changes were observed in stunned myocytes. Increasing frequency increased function, and reducing nitric oxide/cyclic GMP enhanced this relationship. The effect of nitric oxide was diminished by stunning, but this was not related to altered cyclic GMP levels. This suggested changes in effects of cyclic GMP downstream to its production during myocardial stunning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00395-003-0425-8DOI Listing
September 2003