Dr.Naresh Kumar Ahuja | RUHS/ SMS medical college, jaipur.. INDIA (original) (raw)

Papers by Dr.Naresh Kumar Ahuja

Research paper thumbnail of Growth and biochemical changes in Acer oblongum Wall. seedlings under short-term moisture stress

Research paper thumbnail of Acetylation of cardiac histones and expression of histone regulated genes can be modulated through fluid resuscitation in a swine model of hemorrhage

Journal of The American College of Surgeons, Sep 1, 2005

No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2005 American College of Surgeons. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site ...

Research paper thumbnail of Steroids and related studies. Part 44. 17a-Methyl-3β-(N-pyrrolidinyl)17a-aza-D-homo-5α-androstane bis(methiodide)(dihydrochandonium iodide) and certain other analogues of chandonium iodide

Journal of the Chemical Society, 1979

The bisquaternary analogues 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bismethio... more The bisquaternary analogues 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bismethiodide (dihydrochandonium iodide)(4), 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bisethiodide (5), 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homoandrost-5-ene bisethiodide (2), and 17a-ethyl-3β-(N-pyrrolidinyl)-17a-aza-D-homoandrost-5-ene bisethiodide (3) related to chandonium iodide (1) have been prepared. 5,6-Saturation and increase in 'onium bulk decrease the neuromuscular blocking potency; however, dihydrochandonium iodide (4) appears to be a promising compound for further study.

Research paper thumbnail of The Imperfect International Sales Law

Maandblad voor Vermogensrecht, 2019

Bridging the Gap: The CISG as a Successful Legal Hybrid between Common Law and Civil Law?', in Fr... more Bridging the Gap: The CISG as a Successful Legal Hybrid between Common Law and Civil Law?', in Francisco de Elizalde (ed.), Uniform Rules for European Contract Law?-A Critical Assessment?, Hart 2018, p. 156. 2. However, it seems to be that in Dutch practice the application of the CISG is often (without sufficiently good legal reasons) excluded. See for the application of the CISG in the Netherlands in general R.I.V.F. Bertrams and S.A. Kruisinga, Overeenkomsten in het internationaal privaatrecht en het Weens koopverdrag, 6th edn.

Research paper thumbnail of Profound hypothermia is superior to ultra-profound hypothermia in improving survival in a swine model of lethal hemorrhage

Journal of Surgical Research, 2006

Background: Medical errors during surgery are not well studied. To define risk factors associated... more Background: Medical errors during surgery are not well studied. To define risk factors associated with this type of error, we performed a case control analysis. Methods: We retrospectively reviewed medical records involving the ICD-9 code (998.4) for unintentional foreign object remaining in the body during surgery and incident reports gathered by the Department of Risk Management over a 10 year period from 1996 to 2005. Each case was then matched with three randomly selected controls (108 control patients total) that underwent the same type of operation during the same time period. Results: Thirty-six patients had retained foreign objects (42% sponges and 53% instruments). The abdominal cavity was most commonly involved (39%) followed by the thoracic cavity (22%) although no body cavity remained uninvolved. Eleven patients required readmission (33%), thirty patients required reoperation (83%), and there was no mortality. When compared to controls, patients with retained foreign objects were more likely to have had a longer operation (207 minutes vs. 164 minutes, pϭ0.006), a greater number of major surgical procedures at the same time (2.3 vs. 1.6, pϭ0.01) performed by multiple surgical teams (11% vs. 3%, pϭ0.05), and more likely to have had an incorrect instrument/ sponge count recorded (11% vs. 2%, pϭ0.03). In multivariate analysis, factors associated with a significantly higher risk of retained foreign objects were the total number of major procedures performed (OR 1.5, [95% CI, 1.1-2.1], pϭ0.02), and an incorrect count (OR 15.8, [95% CI, 1.2-218.6], pϭ0.03). Conclusion: Retained foreign objects after surgery are associated with multiple major surgical procedures being performed at the same time and an incorrect instrument or sponge count. Identification of these risk factors using case-control analysis may influence operating room policy and reduce these types of errors.

Research paper thumbnail of Formulation Development of Efavirenz Tablets Employing HP Β Cyclodextrin-PVP K30-SLS: A Factorial Study

international journal of chemical sciences, 2012

Efavirenz, a widely prescribed anti retroviral drug belongs to class IΙ under BCS and exhibit low... more Efavirenz, a widely prescribed anti retroviral drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating efavirenz-βCD-PVP K30/SLS inclusion complexes into tablets and to evaluate the effects of βCD, PVP K30and SLS on the dissolution rate and dissolution efficiency of efavirenz tablets in a 2 3 factorial study. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug-βCD-PVP K30/ SLS inclusion complexes. Drug-βCD-PVP K30/ SLS inclusion complexes were prepared by kneading method. Tablets each containing 50 mg of efavirenz were prepared by wet granulation and direct compression methods employing various βCD complexes as per 2 3 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz tablets formulated employing dug-βCD-PVP K30/ SLS inclusion complexes and prepared by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Efavirenz dissolution was rapid and higher from the tablets formulated employing drug-βCD-PVP K30 /or SLS inclusion complexes when compared to the tablets containing efavirenz alone in both wet granulation and direct compression methods. The individual as well as combined effects of the three factors involved i.e., βCD (factor A), PVP K30(factor B) and SLS(factor C) were highly significant (P< 0.01) in enhancing the dissolution rate (K 1) and dissolution efficiency (DE 30) of efavirenz in both wet granulation and direct compression methods. Among the three factors βCD (factor A) gave highest enhancement in the dissolution rate (K 1) and dissolution efficiency (DE 30) of efavirenz tablets in both wet granulation and direct compression methods. SLS (factor C) alone gave low dissolution rate in both wet granulation and direct compression methods .Overall direct compression method gave higher dissolution rates (K 1) and dissolution efficiency (DE 30) values than the wet granulation method in all the cases. Combination of βCD with either PVP K30 or SLS or both gave a significantly higher dissolution rate (K 1) of efavirenz in both wet granulation and direct compression methods. Hence a combination of βCD with either PVP K30 or SLS or both is recommended to enhance the dissolution rate and efficiency of efavirenz tablets.

Research paper thumbnail of Novel Nano Therapeutic Materials for the Effective Treatment of Rheumatoid Arthritis-Recent Insights

International Journal of Applied Pharmaceutics, Nov 7, 2021

Recent advances in science and technology and greatly modified the way we stumble on, deal with a... more Recent advances in science and technology and greatly modified the way we stumble on, deal with and prevent special diseases in all components of human lifestyles. Rheumatoid arthritis (RA) is the most not unusual complex multifactorial joint related autoimmune, chronic, severe systemic inflammatory ailment with unknown etiology completed with increased cardiovascular risks. It is regularly associated with critical synovial joint inflammation, autoantibody production, cartilage/bone tissue destruction, cardiovascular, pulmonary, skeletal disorders and massive inflammatory infiltration which might in the end motive extreme disability, huge complications, premature mortality and decreased life quality. Pro-inflammatory cytokines like IL-1, IL-6, IL-8 and IL-10 were dependable for the induction of inflammation in RA patients. It has a global occurrence of around 1% with the incidence among women being 2-3 times extra in men. Preclinical RA, genetic variables, and environmental factors have all been linked to the disease's etiology. Because there is no known cure for RA, the primary goal of treatment is to achieve the shortest possible illness duration and, if possible, rehabilitation. Current clinical remedies of RA display numerous drawbacks which include excessive doses, common administration, speedy metabolism, bad absorption, low responsiveness, higher cost and serious side consequences. These obstacles have inspired extremely good growth of the studies and to enhance those obstacles, nanoparticles that are able to encapsulating and protecting tablets from degradation earlier than they reach the target site in vivo, might also function drug delivery structures. Bioavailability and therapeutic bioactivity can be improved, and limited emphasis on damaged joints can be allowed. The current study provides a platform for different lipid nanoparticle methods for RA therapy, using the newly developing field of lipid nanoparticles to improve a targeted theranostic device for RA treatment. This review aims to present the most recent major application of lipid nanoparticles as a biocompatible and biodegradable transport device for improving RA concentration on over free drugs by presenting tissue-specific concentrated on of ligand-controlled drug release by modulating nanoparticle composition. Additionally, we also discuss the pivotal demanding situations to be addressed, as well as destiny views. Therefore, it is feasible to claim that nanoparticles will, within the near future, play a critical role in advanced treatment and affected person-particular cures for human diseases which include RA.

Research paper thumbnail of Formulation and Evaluation of Lansoprazole Niosome

The niosomes formulation has got various advantages over conventional dosage forms; these stay in... more The niosomes formulation has got various advantages over conventional dosage forms; these stay in the blood for longer time then conventional and can thus greatly improve the therapeutic effect of drug. In many diseases (e.g. cancer) a considerable therapeutic advantage could be gained if drugs were delivered in selective and controlled manner to their target sites. The noisome are prepared by reverse phase evaporation method using a homogenizers. Non-ionic surfactant based vesicles used as vesicles for drug formulation have been found to reduce the systemic toxicity of many drugs. Lansoprazole was selected as candidate drug, it is antacid and antiulcer agents. Niosomes are characterized for its size rang, entrapment efficiency and in-vitro release of drug. For release study the phosphate buffer saline pH 8.6 was used and the samples were assayed by UV.

Research paper thumbnail of Formulation and evaluation of diclofenac sodium gel by using natural polymer

Abstract In this investigation, Diclofenac sodium gels were formulated employing Sodium carboxyme... more Abstract In this investigation, Diclofenac sodium gels were formulated employing Sodium carboxymethyl hydroxypropyl guar and Hydroxypropyl methylcellulose as gelling agents. Hydroxypropyl methylcellulose (K4M) was employed at 5% w/w strength whereas, Sodium carboxymethyl hydroxypropyl ...

Research paper thumbnail of Analysis of After Impact Characteristics and Structural Optimization of CFRP Composite Plate

AIAA Scitech 2021 Forum, 2021

First of all, I would like to express my great gratitude to Dr. Mandar Kulkarni who has brought m... more First of all, I would like to express my great gratitude to Dr. Mandar Kulkarni who has brought me into the project and provided me continuous help through this research journey. I would never forget those weekly meetings whenever I had any questions or ideas, he would patiently give me elaborate answers and feasible planning for the next steps. Also, he would always make a quick response to me through endless email communication. His erudition and great enthusiasm helped me conquer the challenges and impel my thesis forward till completion. Special thanks to Dr. David Sypeck for spending months training me getting familiar with the testing equipment and helped me to finish the low-velocity impact test and understand the technique of the compression test. Without his help, my research would be stuck at the beginning. Also, I want to thank Dr. Marwan Al-Haik who helped me learn the X-Ray imaging testing and understand the failure mechanism of composite materials. I am also grateful to Dr. Sirish Namilae who providing the equipment and tools for the laminates fabrication. Besides, I must thank Christian Aparicio from MSC Corporation for giving me the professional guidance of optimization methods. At last, my greatest gratitude gives to my dear parents and my close friends. Whenever I'm feeling down, they are always my best confessors and confidants. Their care and understanding help me regain confidence and be able to achieve my dream.

Research paper thumbnail of Impact of resuscitation strategies on the acetylation status of cardiac histones in a swine model of hemorrhage

Resuscitation, 2008

Chromatin remodeling through histone acetylation is a key control mechanism in gene transcription... more Chromatin remodeling through histone acetylation is a key control mechanism in gene transcription. We have shown previously that fluid resuscitation in rodents is coupled with highly structured post-translational modifications of cardiac histones. The current experiment was performed to validate this concept in a clinically relevant large animal model of hemorrhage and resuscitation, and to correlate the changes in histone acetylation with altered expression of immediate-early response genes. Yorkshire swine (n=49, 7/group, weight=40-58kg) were subjected to combined uncontrolled and controlled hemorrhage (40% of estimated blood volume) and randomly assigned to the following resuscitation groups: (1) 0.9% saline (NS), (2) racemic lactated Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (dl-LR), (3) l-isomer lactated Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (l-LR), (4) Ketone Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (KR), (5) 6% hetastarch in saline (Hespan). KR contained an equimolar substitution of lactate with beta-hydroxybutyrate. No hemorrhage (NH) and no resuscitation (NR) groups were included as controls. Cardiac protein was used in Western blotting to analyze total protein acetylation and histone acetylation specifically. Lysine residue-specific acetylation of histone subunits H3 and H4 was further evaluated. In addition, Chromatin Immunoprecipitation (ChIP) technique was used to separate the DNA bound to acetylated histones (H3 and H4 subunits), followed by measurement of genes that are altered by hemorrhage/resuscitation, including immediate-early response genes (c-fos and c-myc), and heat shock protein (HSP) 70. The type of fluid used for resuscitation influenced the patterns of cardiac histone acetylation. Resuscitation with dl-LR and KR induced hyperacetylation on H3K9. KR resuscitation was also associated with increased acetylation on H3K14 and H4K5, and hypoacetylation on H3K18. The expression of genes was also fluid specific, with the largest number of changes following KR resuscitation (increased c-fos and c-myc, HSP 70 linked with H3; and increased c-myc linked with H4). Among the histone subunits studied, altered H3 acetylations were associated with the majority of changes in immediate-early gene expression. Acetylation status of cardiac histones, affected by hemorrhage, is further modulated by resuscitation producing a fluid-specific code that is preserved in different species. Resuscitation with KR causes histone acetylation at the largest number of lysine sites (predominately H3 subunit), and has the most pronounced impact on the transcriptional regulation of selected (immediate-early response) genes.

Research paper thumbnail of Predicting Quality of Life Six Months After Traumatic Injury

The Journal of Trauma: Injury, Infection, and Critical Care, 2005

Background: Many factors are known to impact quality of life (QoL) after injury, but predictors o... more Background: Many factors are known to impact quality of life (QoL) after injury, but predictors of diminished QoL and the time course of recovery remain incompletely understood. This study examines predictors and correlates of QoL measured by the Short Form-36 (SF-36) one and six months postinjury. Methods: Adults with nonneurologic blunt injury were prospectively enrolled. Demographic, injury, and socioeconomic data were collected. Patients were assessed with functional and psychologic measures. In all, 196 patients had 1-month data and 123 had 6-month data available. Scores were compared at each time point and also to population norms using t-tests. Multiple regression techniques were used to identify associations between the physical and mental component scores (PCS & MCS) of the SF-36 and patient characteristics. Results: PCS scores improved significantly (32.8 ؎ 0.9 versus 41.3 ؎ 1.0, p < 0.05) whereas MCS scores (47.5 ؎ 1.1 versus 47.2 ؎ 1.1, p ‫؍‬ NS) did not. Both remained significantly below population norms. Functional Independence Measure (FIM) at one month was predictive of PCS at 6 months. Posttraumatic stress disorder (PTSD) was predictive of lower MCS, and depression was associated with poor MCS. Injury Severity Score was not associated with PCS or MCS. Conclusions: Overall physical and mental QoL measured by the SF-36 remains significantly below population norms 6 months after traumatic injury. It is possible to identify patients at risk for diminished QoL early during recovery by screening for functional status, PTSD, social support, and depression. Interventions to address these areas should be further studied with respect to their impact on long-term QoL.

Research paper thumbnail of Hepatic and Pulmonary Apoptosis After Hemorrhagic Shock in Swine Can Be Reduced Through Modifications of Conventional Ringer???s Solution

The Journal of Trauma: Injury, Infection, and Critical Care, 2006

Background: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in... more Background: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of D-lactate. Methods: Yorkshire swine (n ‫؍‬ 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n ‫؍‬ 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-␣, IL-1,-6,-10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. Results: All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six-and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. Conclusions: In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.

Research paper thumbnail of Testing of Modified Zeolite Hemostatic Dressings in a Large Animal Model of Lethal Groin Injury

The Journal of Trauma: Injury, Infection, and Critical Care, 2006

Background: We have previously identified a granular zeolite hemostat (ZH) as an effective agent ... more Background: We have previously identified a granular zeolite hemostat (ZH) as an effective agent for control of severe bleeding, and it is currently being used by the US troops in the battlefield. ZH causes an exothermic reaction on application, which theoretically can be decreased by altering its chemical composition or changing its physical properties. However, the effect of these alterations on the hemostatic efficacy is unknown. We tested modified zeolites and a chitosan based dressing against controls in a swine model of battlefield injury. Methods: A complex groin injury was created in 60 swine (40-55 kg). This included semi-transection of the proximal thigh (level of inguinal ligament), and complete division of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3-5) SD ؉ chemically modified ZHs, where calcium was substituted with sodium (Na), barium (Ba), or silver (Ag), respectively, (6) SD ؉ physically modified ZH, where "beads" were packaged in a fabric bag, (7) SD ؉ chitosan based dressing (CD). Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch over 30 minutes). Survival for 180 minutes was the primary endpoint for this study. In addition, blood loss, wound temperatures, and histologic tissue damage were recorded. Results: Mortality in the group that was treated with the application of bagged ZH was 10% versus 100% in the no dressing group and 50% in the SD group (p < 0.05 vs. ND and SD groups). The Na ZH group had a mortality rate of 43%, whereas application of Ba and Ag substituted zeolites, and CD were associated with a mortality rate of 25%. Ionic substitution of zeolite decreased the in vivo temperature peak by 5 to 10°C. No histologic evidence of tissue necrosis was noted in this experiment. Conclusions: The use of zeolite hemostat can control hemorrhage and dramatically reduce mortality from a lethal groin wound. Modifications of zeolite hemostat can decrease the exothermic reaction and attenuate tissue damage.

Research paper thumbnail of Profound Hypothermic Cardiopulmonary Bypass Facilitates Survival Without a High Complication Rate in a Swine Model of Complex Vascular, Splenic, and Colon Injuries

Journal of the American College of Surgeons, 2007

Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorr... more Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorrhagic shock can improve survival from lethal injuries, but the impact of hypothermia on bleeding and infectious complications has not been completely determined. Uncontrolled hemorrhage was induced in 26 swine (95 to 135 lbs) by creating an iliac artery and vein injury, and 30 minutes later, by lacerating the descending thoracic aorta. Through a left thoracotomy approach, profound total body hypothermia (10 degrees C) was induced (2 degrees C/min) by infusing cold organ preservation solution into the aorta. The experimental groups were: vascular injuries alone (group 1, n=10), vascular and colon injuries (group 2, n=8), and vascular, colon, and splenic injuries (group 3, n=8). All injuries were repaired during 60 minutes of low-flow cardiopulmonary bypass (CPB) with hemodilution and profound hypothermia; then the animals were slowly rewarmed (0.5 degrees C/min) back to normothermia. Survivors were monitored for 6 weeks for postoperative bleeding, neurologic deficits, cognitive function (learning new skills), organ dysfunction, and septic complications. Six-week survival rates were 90% in group 1, 87.5% in group 2, and 75% in group 3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). One animal in each group died from acute cardiac failure during the early postoperative phase. Splenic salvage was possible in all animals, and none required complete splenectomy for hemorrhage control. All surviving animals were neurologically intact, displayed normal learning capacity, and had no longterm organ dysfunction. None of the animals had postoperative hemorrhage or experienced septic complications. One animal in group 3 died on the ninth postoperative day because of bowel obstruction (volvulus). Induction of profound hypothermia can preserve the viability of key organs during repair of lethal injuries. This strategy can be used even in the presence of solid organ and bowel injuries to improve survival, without any considerable increase in postoperative complication rates.

Research paper thumbnail of Profound Hypothermia Protects Neurons and Astrocytes, and Preserves Cognitive Functions in a Swine Model of Lethal Hemorrhage1

Journal of Surgical Research, 2005

Background. Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended anim... more Background. Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of this strategy on neuronal and astroglial damage in a swine model of lethal hemorrhage. Furthermore, our goal was to correlate the histological changes in the brain with neurological outcome, and the levels of circulating brain specific markers. Materials and Methods. Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later by laceration of the thoracic aorta. Through a thoracotomy approach, organ preservation fluid was infused into the aorta using a roller pump. Experimental groups included normothermic controls (no cooling, NC), and groups where hypothermia was induced at three different rates: 0.5°C/min (slow, SC), 1°C/min (medium, MC), or 2°C/min (fast, FC). Profound hypothermia (core temperature of 10°C) was maintained for 60 min for repair of vascular injuries, after which the animals were re-warmed (0.5°C/min) and resuscitated on cardiopulmonary bypass (CPB). Circulating levels of neuron specific enolase (NSE) and S-100␤ were serially measured as markers of damage to neurons and astrocytes, respectively. Light microscopy and quantitative immunohistochemical techniques were used to evaluate hippocampal CA1 area and caudate putamen for neuronal injury and astrogliosis (astrocyte hyperplasia/hypertrophy). Surviving animals were observed for 6 weeks and neurological status was documented on an objective scale, and cognitive functions were evaluated using a technique based upon the concept of operant conditioning. Results. Normothermic arrest resulted in clinical brain death in all of the animals. None of the surviving hypothermic animals displayed any neurological deficits or cognitive impairment. On histological examination, normothermic animals were found to have ischemic changes in the neurons and astrocytes (hypertrophy). In contrast, all of the hypothermic animals had histologically normal brains. The circulating levels of brain specific proteins did not correlate with the degree of brain damage. The changes in NSE levels were not statistically significant, whereas S-100␤ increased in the circulation after CPB, largely independent of the temperature modulation. Conclusions. Profound hypothermia can preserve viability of neurons and astrocytes during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurological outcome following severe shock. Circulating markers of central nervous system injury did not correlate with the actual degree of brain damage in this model.

Research paper thumbnail of Steroids and related studies: part 90 — certain new azasteroidal bisquaternary neuromuscular blockers

European Journal of Medicinal Chemistry, 1993

Abstract Bisquaternary azasteroids HS-1177 7 and HS-1181 8 , structurally resembling chandonium 2... more Abstract Bisquaternary azasteroids HS-1177 7 and HS-1181 8 , structurally resembling chandonium 2 in rings A and B characteristics, and HS-1184 6 , in part resembling HS-467 1 have been prepared and characterised. All 3 compounds, each possessing 16α-methyltrimethylammonium functions, were prepared as potential neuromuscular blocking agents. They were found to be active but less effective than chandonium.

Research paper thumbnail of Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights

Materials Today Communications, 2018

Rheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune infl... more Rheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA. 1. Introduction Rheumatoid arthritis (RA) is an autoimmune disease characterized with joint pain (functional joint failure), swelling/destruction of bone and cartilage, with an estimated reported global prevalence of around 0.3-1.0 % [1]. RA is the commonest inflammatory arthritis affecting up

Research paper thumbnail of Growth and biochemical changes in Acer oblongum Wall. seedlings under short-term moisture stress

Research paper thumbnail of Acetylation of cardiac histones and expression of histone regulated genes can be modulated through fluid resuscitation in a swine model of hemorrhage

Journal of The American College of Surgeons, Sep 1, 2005

No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2005 American College of Surgeons. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site ...

Research paper thumbnail of Steroids and related studies. Part 44. 17a-Methyl-3β-(N-pyrrolidinyl)17a-aza-D-homo-5α-androstane bis(methiodide)(dihydrochandonium iodide) and certain other analogues of chandonium iodide

Journal of the Chemical Society, 1979

The bisquaternary analogues 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bismethio... more The bisquaternary analogues 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bismethiodide (dihydrochandonium iodide)(4), 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homo-5α-androstane bisethiodide (5), 17a-methyl-3β-(N-pyrrolidinyl)-17a-aza-D-homoandrost-5-ene bisethiodide (2), and 17a-ethyl-3β-(N-pyrrolidinyl)-17a-aza-D-homoandrost-5-ene bisethiodide (3) related to chandonium iodide (1) have been prepared. 5,6-Saturation and increase in 'onium bulk decrease the neuromuscular blocking potency; however, dihydrochandonium iodide (4) appears to be a promising compound for further study.

Research paper thumbnail of The Imperfect International Sales Law

Maandblad voor Vermogensrecht, 2019

Bridging the Gap: The CISG as a Successful Legal Hybrid between Common Law and Civil Law?', in Fr... more Bridging the Gap: The CISG as a Successful Legal Hybrid between Common Law and Civil Law?', in Francisco de Elizalde (ed.), Uniform Rules for European Contract Law?-A Critical Assessment?, Hart 2018, p. 156. 2. However, it seems to be that in Dutch practice the application of the CISG is often (without sufficiently good legal reasons) excluded. See for the application of the CISG in the Netherlands in general R.I.V.F. Bertrams and S.A. Kruisinga, Overeenkomsten in het internationaal privaatrecht en het Weens koopverdrag, 6th edn.

Research paper thumbnail of Profound hypothermia is superior to ultra-profound hypothermia in improving survival in a swine model of lethal hemorrhage

Journal of Surgical Research, 2006

Background: Medical errors during surgery are not well studied. To define risk factors associated... more Background: Medical errors during surgery are not well studied. To define risk factors associated with this type of error, we performed a case control analysis. Methods: We retrospectively reviewed medical records involving the ICD-9 code (998.4) for unintentional foreign object remaining in the body during surgery and incident reports gathered by the Department of Risk Management over a 10 year period from 1996 to 2005. Each case was then matched with three randomly selected controls (108 control patients total) that underwent the same type of operation during the same time period. Results: Thirty-six patients had retained foreign objects (42% sponges and 53% instruments). The abdominal cavity was most commonly involved (39%) followed by the thoracic cavity (22%) although no body cavity remained uninvolved. Eleven patients required readmission (33%), thirty patients required reoperation (83%), and there was no mortality. When compared to controls, patients with retained foreign objects were more likely to have had a longer operation (207 minutes vs. 164 minutes, pϭ0.006), a greater number of major surgical procedures at the same time (2.3 vs. 1.6, pϭ0.01) performed by multiple surgical teams (11% vs. 3%, pϭ0.05), and more likely to have had an incorrect instrument/ sponge count recorded (11% vs. 2%, pϭ0.03). In multivariate analysis, factors associated with a significantly higher risk of retained foreign objects were the total number of major procedures performed (OR 1.5, [95% CI, 1.1-2.1], pϭ0.02), and an incorrect count (OR 15.8, [95% CI, 1.2-218.6], pϭ0.03). Conclusion: Retained foreign objects after surgery are associated with multiple major surgical procedures being performed at the same time and an incorrect instrument or sponge count. Identification of these risk factors using case-control analysis may influence operating room policy and reduce these types of errors.

Research paper thumbnail of Formulation Development of Efavirenz Tablets Employing HP Β Cyclodextrin-PVP K30-SLS: A Factorial Study

international journal of chemical sciences, 2012

Efavirenz, a widely prescribed anti retroviral drug belongs to class IΙ under BCS and exhibit low... more Efavirenz, a widely prescribed anti retroviral drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating efavirenz-βCD-PVP K30/SLS inclusion complexes into tablets and to evaluate the effects of βCD, PVP K30and SLS on the dissolution rate and dissolution efficiency of efavirenz tablets in a 2 3 factorial study. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug-βCD-PVP K30/ SLS inclusion complexes. Drug-βCD-PVP K30/ SLS inclusion complexes were prepared by kneading method. Tablets each containing 50 mg of efavirenz were prepared by wet granulation and direct compression methods employing various βCD complexes as per 2 3 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz tablets formulated employing dug-βCD-PVP K30/ SLS inclusion complexes and prepared by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Efavirenz dissolution was rapid and higher from the tablets formulated employing drug-βCD-PVP K30 /or SLS inclusion complexes when compared to the tablets containing efavirenz alone in both wet granulation and direct compression methods. The individual as well as combined effects of the three factors involved i.e., βCD (factor A), PVP K30(factor B) and SLS(factor C) were highly significant (P< 0.01) in enhancing the dissolution rate (K 1) and dissolution efficiency (DE 30) of efavirenz in both wet granulation and direct compression methods. Among the three factors βCD (factor A) gave highest enhancement in the dissolution rate (K 1) and dissolution efficiency (DE 30) of efavirenz tablets in both wet granulation and direct compression methods. SLS (factor C) alone gave low dissolution rate in both wet granulation and direct compression methods .Overall direct compression method gave higher dissolution rates (K 1) and dissolution efficiency (DE 30) values than the wet granulation method in all the cases. Combination of βCD with either PVP K30 or SLS or both gave a significantly higher dissolution rate (K 1) of efavirenz in both wet granulation and direct compression methods. Hence a combination of βCD with either PVP K30 or SLS or both is recommended to enhance the dissolution rate and efficiency of efavirenz tablets.

Research paper thumbnail of Novel Nano Therapeutic Materials for the Effective Treatment of Rheumatoid Arthritis-Recent Insights

International Journal of Applied Pharmaceutics, Nov 7, 2021

Recent advances in science and technology and greatly modified the way we stumble on, deal with a... more Recent advances in science and technology and greatly modified the way we stumble on, deal with and prevent special diseases in all components of human lifestyles. Rheumatoid arthritis (RA) is the most not unusual complex multifactorial joint related autoimmune, chronic, severe systemic inflammatory ailment with unknown etiology completed with increased cardiovascular risks. It is regularly associated with critical synovial joint inflammation, autoantibody production, cartilage/bone tissue destruction, cardiovascular, pulmonary, skeletal disorders and massive inflammatory infiltration which might in the end motive extreme disability, huge complications, premature mortality and decreased life quality. Pro-inflammatory cytokines like IL-1, IL-6, IL-8 and IL-10 were dependable for the induction of inflammation in RA patients. It has a global occurrence of around 1% with the incidence among women being 2-3 times extra in men. Preclinical RA, genetic variables, and environmental factors have all been linked to the disease's etiology. Because there is no known cure for RA, the primary goal of treatment is to achieve the shortest possible illness duration and, if possible, rehabilitation. Current clinical remedies of RA display numerous drawbacks which include excessive doses, common administration, speedy metabolism, bad absorption, low responsiveness, higher cost and serious side consequences. These obstacles have inspired extremely good growth of the studies and to enhance those obstacles, nanoparticles that are able to encapsulating and protecting tablets from degradation earlier than they reach the target site in vivo, might also function drug delivery structures. Bioavailability and therapeutic bioactivity can be improved, and limited emphasis on damaged joints can be allowed. The current study provides a platform for different lipid nanoparticle methods for RA therapy, using the newly developing field of lipid nanoparticles to improve a targeted theranostic device for RA treatment. This review aims to present the most recent major application of lipid nanoparticles as a biocompatible and biodegradable transport device for improving RA concentration on over free drugs by presenting tissue-specific concentrated on of ligand-controlled drug release by modulating nanoparticle composition. Additionally, we also discuss the pivotal demanding situations to be addressed, as well as destiny views. Therefore, it is feasible to claim that nanoparticles will, within the near future, play a critical role in advanced treatment and affected person-particular cures for human diseases which include RA.

Research paper thumbnail of Formulation and Evaluation of Lansoprazole Niosome

The niosomes formulation has got various advantages over conventional dosage forms; these stay in... more The niosomes formulation has got various advantages over conventional dosage forms; these stay in the blood for longer time then conventional and can thus greatly improve the therapeutic effect of drug. In many diseases (e.g. cancer) a considerable therapeutic advantage could be gained if drugs were delivered in selective and controlled manner to their target sites. The noisome are prepared by reverse phase evaporation method using a homogenizers. Non-ionic surfactant based vesicles used as vesicles for drug formulation have been found to reduce the systemic toxicity of many drugs. Lansoprazole was selected as candidate drug, it is antacid and antiulcer agents. Niosomes are characterized for its size rang, entrapment efficiency and in-vitro release of drug. For release study the phosphate buffer saline pH 8.6 was used and the samples were assayed by UV.

Research paper thumbnail of Formulation and evaluation of diclofenac sodium gel by using natural polymer

Abstract In this investigation, Diclofenac sodium gels were formulated employing Sodium carboxyme... more Abstract In this investigation, Diclofenac sodium gels were formulated employing Sodium carboxymethyl hydroxypropyl guar and Hydroxypropyl methylcellulose as gelling agents. Hydroxypropyl methylcellulose (K4M) was employed at 5% w/w strength whereas, Sodium carboxymethyl hydroxypropyl ...

Research paper thumbnail of Analysis of After Impact Characteristics and Structural Optimization of CFRP Composite Plate

AIAA Scitech 2021 Forum, 2021

First of all, I would like to express my great gratitude to Dr. Mandar Kulkarni who has brought m... more First of all, I would like to express my great gratitude to Dr. Mandar Kulkarni who has brought me into the project and provided me continuous help through this research journey. I would never forget those weekly meetings whenever I had any questions or ideas, he would patiently give me elaborate answers and feasible planning for the next steps. Also, he would always make a quick response to me through endless email communication. His erudition and great enthusiasm helped me conquer the challenges and impel my thesis forward till completion. Special thanks to Dr. David Sypeck for spending months training me getting familiar with the testing equipment and helped me to finish the low-velocity impact test and understand the technique of the compression test. Without his help, my research would be stuck at the beginning. Also, I want to thank Dr. Marwan Al-Haik who helped me learn the X-Ray imaging testing and understand the failure mechanism of composite materials. I am also grateful to Dr. Sirish Namilae who providing the equipment and tools for the laminates fabrication. Besides, I must thank Christian Aparicio from MSC Corporation for giving me the professional guidance of optimization methods. At last, my greatest gratitude gives to my dear parents and my close friends. Whenever I'm feeling down, they are always my best confessors and confidants. Their care and understanding help me regain confidence and be able to achieve my dream.

Research paper thumbnail of Impact of resuscitation strategies on the acetylation status of cardiac histones in a swine model of hemorrhage

Resuscitation, 2008

Chromatin remodeling through histone acetylation is a key control mechanism in gene transcription... more Chromatin remodeling through histone acetylation is a key control mechanism in gene transcription. We have shown previously that fluid resuscitation in rodents is coupled with highly structured post-translational modifications of cardiac histones. The current experiment was performed to validate this concept in a clinically relevant large animal model of hemorrhage and resuscitation, and to correlate the changes in histone acetylation with altered expression of immediate-early response genes. Yorkshire swine (n=49, 7/group, weight=40-58kg) were subjected to combined uncontrolled and controlled hemorrhage (40% of estimated blood volume) and randomly assigned to the following resuscitation groups: (1) 0.9% saline (NS), (2) racemic lactated Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (dl-LR), (3) l-isomer lactated Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (l-LR), (4) Ketone Ringer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (KR), (5) 6% hetastarch in saline (Hespan). KR contained an equimolar substitution of lactate with beta-hydroxybutyrate. No hemorrhage (NH) and no resuscitation (NR) groups were included as controls. Cardiac protein was used in Western blotting to analyze total protein acetylation and histone acetylation specifically. Lysine residue-specific acetylation of histone subunits H3 and H4 was further evaluated. In addition, Chromatin Immunoprecipitation (ChIP) technique was used to separate the DNA bound to acetylated histones (H3 and H4 subunits), followed by measurement of genes that are altered by hemorrhage/resuscitation, including immediate-early response genes (c-fos and c-myc), and heat shock protein (HSP) 70. The type of fluid used for resuscitation influenced the patterns of cardiac histone acetylation. Resuscitation with dl-LR and KR induced hyperacetylation on H3K9. KR resuscitation was also associated with increased acetylation on H3K14 and H4K5, and hypoacetylation on H3K18. The expression of genes was also fluid specific, with the largest number of changes following KR resuscitation (increased c-fos and c-myc, HSP 70 linked with H3; and increased c-myc linked with H4). Among the histone subunits studied, altered H3 acetylations were associated with the majority of changes in immediate-early gene expression. Acetylation status of cardiac histones, affected by hemorrhage, is further modulated by resuscitation producing a fluid-specific code that is preserved in different species. Resuscitation with KR causes histone acetylation at the largest number of lysine sites (predominately H3 subunit), and has the most pronounced impact on the transcriptional regulation of selected (immediate-early response) genes.

Research paper thumbnail of Predicting Quality of Life Six Months After Traumatic Injury

The Journal of Trauma: Injury, Infection, and Critical Care, 2005

Background: Many factors are known to impact quality of life (QoL) after injury, but predictors o... more Background: Many factors are known to impact quality of life (QoL) after injury, but predictors of diminished QoL and the time course of recovery remain incompletely understood. This study examines predictors and correlates of QoL measured by the Short Form-36 (SF-36) one and six months postinjury. Methods: Adults with nonneurologic blunt injury were prospectively enrolled. Demographic, injury, and socioeconomic data were collected. Patients were assessed with functional and psychologic measures. In all, 196 patients had 1-month data and 123 had 6-month data available. Scores were compared at each time point and also to population norms using t-tests. Multiple regression techniques were used to identify associations between the physical and mental component scores (PCS & MCS) of the SF-36 and patient characteristics. Results: PCS scores improved significantly (32.8 ؎ 0.9 versus 41.3 ؎ 1.0, p < 0.05) whereas MCS scores (47.5 ؎ 1.1 versus 47.2 ؎ 1.1, p ‫؍‬ NS) did not. Both remained significantly below population norms. Functional Independence Measure (FIM) at one month was predictive of PCS at 6 months. Posttraumatic stress disorder (PTSD) was predictive of lower MCS, and depression was associated with poor MCS. Injury Severity Score was not associated with PCS or MCS. Conclusions: Overall physical and mental QoL measured by the SF-36 remains significantly below population norms 6 months after traumatic injury. It is possible to identify patients at risk for diminished QoL early during recovery by screening for functional status, PTSD, social support, and depression. Interventions to address these areas should be further studied with respect to their impact on long-term QoL.

Research paper thumbnail of Hepatic and Pulmonary Apoptosis After Hemorrhagic Shock in Swine Can Be Reduced Through Modifications of Conventional Ringer???s Solution

The Journal of Trauma: Injury, Infection, and Critical Care, 2006

Background: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in... more Background: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of D-lactate. Methods: Yorkshire swine (n ‫؍‬ 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n ‫؍‬ 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-␣, IL-1,-6,-10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. Results: All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six-and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. Conclusions: In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.

Research paper thumbnail of Testing of Modified Zeolite Hemostatic Dressings in a Large Animal Model of Lethal Groin Injury

The Journal of Trauma: Injury, Infection, and Critical Care, 2006

Background: We have previously identified a granular zeolite hemostat (ZH) as an effective agent ... more Background: We have previously identified a granular zeolite hemostat (ZH) as an effective agent for control of severe bleeding, and it is currently being used by the US troops in the battlefield. ZH causes an exothermic reaction on application, which theoretically can be decreased by altering its chemical composition or changing its physical properties. However, the effect of these alterations on the hemostatic efficacy is unknown. We tested modified zeolites and a chitosan based dressing against controls in a swine model of battlefield injury. Methods: A complex groin injury was created in 60 swine (40-55 kg). This included semi-transection of the proximal thigh (level of inguinal ligament), and complete division of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3-5) SD ؉ chemically modified ZHs, where calcium was substituted with sodium (Na), barium (Ba), or silver (Ag), respectively, (6) SD ؉ physically modified ZH, where "beads" were packaged in a fabric bag, (7) SD ؉ chitosan based dressing (CD). Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch over 30 minutes). Survival for 180 minutes was the primary endpoint for this study. In addition, blood loss, wound temperatures, and histologic tissue damage were recorded. Results: Mortality in the group that was treated with the application of bagged ZH was 10% versus 100% in the no dressing group and 50% in the SD group (p < 0.05 vs. ND and SD groups). The Na ZH group had a mortality rate of 43%, whereas application of Ba and Ag substituted zeolites, and CD were associated with a mortality rate of 25%. Ionic substitution of zeolite decreased the in vivo temperature peak by 5 to 10°C. No histologic evidence of tissue necrosis was noted in this experiment. Conclusions: The use of zeolite hemostat can control hemorrhage and dramatically reduce mortality from a lethal groin wound. Modifications of zeolite hemostat can decrease the exothermic reaction and attenuate tissue damage.

Research paper thumbnail of Profound Hypothermic Cardiopulmonary Bypass Facilitates Survival Without a High Complication Rate in a Swine Model of Complex Vascular, Splenic, and Colon Injuries

Journal of the American College of Surgeons, 2007

Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorr... more Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorrhagic shock can improve survival from lethal injuries, but the impact of hypothermia on bleeding and infectious complications has not been completely determined. Uncontrolled hemorrhage was induced in 26 swine (95 to 135 lbs) by creating an iliac artery and vein injury, and 30 minutes later, by lacerating the descending thoracic aorta. Through a left thoracotomy approach, profound total body hypothermia (10 degrees C) was induced (2 degrees C/min) by infusing cold organ preservation solution into the aorta. The experimental groups were: vascular injuries alone (group 1, n=10), vascular and colon injuries (group 2, n=8), and vascular, colon, and splenic injuries (group 3, n=8). All injuries were repaired during 60 minutes of low-flow cardiopulmonary bypass (CPB) with hemodilution and profound hypothermia; then the animals were slowly rewarmed (0.5 degrees C/min) back to normothermia. Survivors were monitored for 6 weeks for postoperative bleeding, neurologic deficits, cognitive function (learning new skills), organ dysfunction, and septic complications. Six-week survival rates were 90% in group 1, 87.5% in group 2, and 75% in group 3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). One animal in each group died from acute cardiac failure during the early postoperative phase. Splenic salvage was possible in all animals, and none required complete splenectomy for hemorrhage control. All surviving animals were neurologically intact, displayed normal learning capacity, and had no longterm organ dysfunction. None of the animals had postoperative hemorrhage or experienced septic complications. One animal in group 3 died on the ninth postoperative day because of bowel obstruction (volvulus). Induction of profound hypothermia can preserve the viability of key organs during repair of lethal injuries. This strategy can be used even in the presence of solid organ and bowel injuries to improve survival, without any considerable increase in postoperative complication rates.

Research paper thumbnail of Profound Hypothermia Protects Neurons and Astrocytes, and Preserves Cognitive Functions in a Swine Model of Lethal Hemorrhage1

Journal of Surgical Research, 2005

Background. Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended anim... more Background. Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of this strategy on neuronal and astroglial damage in a swine model of lethal hemorrhage. Furthermore, our goal was to correlate the histological changes in the brain with neurological outcome, and the levels of circulating brain specific markers. Materials and Methods. Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later by laceration of the thoracic aorta. Through a thoracotomy approach, organ preservation fluid was infused into the aorta using a roller pump. Experimental groups included normothermic controls (no cooling, NC), and groups where hypothermia was induced at three different rates: 0.5°C/min (slow, SC), 1°C/min (medium, MC), or 2°C/min (fast, FC). Profound hypothermia (core temperature of 10°C) was maintained for 60 min for repair of vascular injuries, after which the animals were re-warmed (0.5°C/min) and resuscitated on cardiopulmonary bypass (CPB). Circulating levels of neuron specific enolase (NSE) and S-100␤ were serially measured as markers of damage to neurons and astrocytes, respectively. Light microscopy and quantitative immunohistochemical techniques were used to evaluate hippocampal CA1 area and caudate putamen for neuronal injury and astrogliosis (astrocyte hyperplasia/hypertrophy). Surviving animals were observed for 6 weeks and neurological status was documented on an objective scale, and cognitive functions were evaluated using a technique based upon the concept of operant conditioning. Results. Normothermic arrest resulted in clinical brain death in all of the animals. None of the surviving hypothermic animals displayed any neurological deficits or cognitive impairment. On histological examination, normothermic animals were found to have ischemic changes in the neurons and astrocytes (hypertrophy). In contrast, all of the hypothermic animals had histologically normal brains. The circulating levels of brain specific proteins did not correlate with the degree of brain damage. The changes in NSE levels were not statistically significant, whereas S-100␤ increased in the circulation after CPB, largely independent of the temperature modulation. Conclusions. Profound hypothermia can preserve viability of neurons and astrocytes during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurological outcome following severe shock. Circulating markers of central nervous system injury did not correlate with the actual degree of brain damage in this model.

Research paper thumbnail of Steroids and related studies: part 90 — certain new azasteroidal bisquaternary neuromuscular blockers

European Journal of Medicinal Chemistry, 1993

Abstract Bisquaternary azasteroids HS-1177 7 and HS-1181 8 , structurally resembling chandonium 2... more Abstract Bisquaternary azasteroids HS-1177 7 and HS-1181 8 , structurally resembling chandonium 2 in rings A and B characteristics, and HS-1184 6 , in part resembling HS-467 1 have been prepared and characterised. All 3 compounds, each possessing 16α-methyltrimethylammonium functions, were prepared as potential neuromuscular blocking agents. They were found to be active but less effective than chandonium.

Research paper thumbnail of Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights

Materials Today Communications, 2018

Rheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune infl... more Rheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA. 1. Introduction Rheumatoid arthritis (RA) is an autoimmune disease characterized with joint pain (functional joint failure), swelling/destruction of bone and cartilage, with an estimated reported global prevalence of around 0.3-1.0 % [1]. RA is the commonest inflammatory arthritis affecting up