Publications by authors named "Syed A Rizvi"

69 Publications

The Deleterious Effects of COVID-19 in the Peripartum Period: A Case Report.

Pediatr Rep 2021 Jun 16;13(2):334-339. Epub 2021 Jun 16.

Department of Pharmaceutical Sciences, Hampton University School of Pharmacy, Hampton, VA 23669, USA.

While the Coronavirus Disease 2019 (COVID-19) pandemic continues to wreak havoc across the nation and the globe as one of the most significant global health crises of our time, recent attention has been turned to the effects of COVID-19 on pregnancy and the puerperium. Although most cases have been asymptomatic, for some patients, the disease may be accompanied by serious complications such as pneumonia, acute respiratory distress, multi organ failure, and death. Several case studies have noted that patients with co-morbidities are at a significant risk of these complications. In a recent systematic review and meta-analysis, authors conclude that cardiovascular disease was associated with increased composite poor outcome in patients with COVID-19. The following case report highlights the multi-system complications and severity of symptoms that can take place after childbirth in a patient with co-morbid obstetric and prenatal conditions and an initially asymptomatic COVID-19 infection.
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http://dx.doi.org/10.3390/pediatric13020041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293368PMC
June 2021

A Randomized Controlled Pilot Trial to Test the Efficacy of Intranasal Chlorpheniramine Maleate With Xylitol for the Treatment of Allergic Rhinitis.

Cureus 2021 Mar 31;13(3):e14206. Epub 2021 Mar 31.

Pulmonary Critical Care, Aventura Hospital and Medical Center, Aventura, USA.

The prevalence of allergic rhinitis (AR), including symptoms of sneezing, nasal itching, airflow obstruction, and nasal discharge caused by histamine and immunoglobulin E (IgE)-mediated reactions, is ~30% in the U.S. Recent studies seem to suggest that the allergic inflammatory processes in AR may be induced by the interaction between an allergen (trigger) and the nasal microbiome (substrate). In this study, we have identified two agents with antihistaminic and microbiome-modulating characteristics that can be administered intranasally, namely, chlorpheniramine maleate (CPM) and xylitol (X). This study aimed to test the efficacy of intranasal CPM plus xylitol (CPM+X) nasal for the treatment of AR in an outpatient setting. A multicenter, randomized, double-blind, 30-day pilot study was conducted during the spring of 2019. After starting five days of placebo therapy (run-in period), patients with moderate-to-severe AR nasal symptoms were randomized to treatment with CPM+X (n=16) spray and nasal saline placebo (PLB; n=13). Both treatments were administered in the form of one spray dose (~100 µL of the solution containing 1.25 mg CPM) per nostril twice a day. Outcome variables were the changes in visual analog scale (VAS) and daily symptoms score (DSS) at days 1, 5, 10, 15, 25, and 30 after the initiation of the treatment. ANOVA (analysis of variance) with repeated revealed a significant treatment-by-time interaction such that the CPM+X group had a significant decrease (p < 0.05) in both DSS (∆-3.0 ± 2.7) and VAS (∆-3.8 ± 2.0) scores compared to PLB after 30 days. The difference in DSS and VAS scores between the groups was evident just after five days (day 10) of using CPM+X. The CPM+X scores were significantly lower (p < 0.008) starting from day 10 compared with day 1, whereas there were no statistically significant (p > 0.008) changes in the PLB during the 30-day treatment window. The present data suggest that nasal CPM+X use effectively improves AR symptoms. A large-scale study of the long-term effects of CPM+X for the treatment of other chronic respiratory disorders and the potential microbiome-modulating effects warrants further investigation.
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http://dx.doi.org/10.7759/cureus.14206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010914PMC
March 2021

Characterization and Applications of Colloidal Systems as Versatile Drug Delivery Carriers for Parenteral Formulations.

Pharmaceuticals (Basel) 2021 Jan 29;14(2). Epub 2021 Jan 29.

School of Pharmacy, Hampton University, Hampton, VA 23668, USA.

Preparing a suitable formulation for parenteral administration is already a difficult task; this, coupled with poor water-soluble new chemical entity (NCE), complicates this situation even further. There are several methodologies available to enhance water solubility, but this alone does not entail successful formulation. Making a micro/nano emulsion with a suitable surfactant not only increases the drug solubility but also the cell membrane permeability. Thus, not only biopharmaceutic classification system (BCS)-II (low solubility compounds) but also BCS-III (low permeability) and BCS-IV drugs (low solubility and low permeability) can be further exploited. Those drug candidates otherwise will not move further in NCE evaluation or clinical trials. This succinct review article delves into various aspects of biphasic micro/nano emulsion systems for parenteral drug delivery including the structure of the biphasic colloidal systems, characterization parameters, stability issues, regulatory considerations, and applications in life sciences.
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http://dx.doi.org/10.3390/ph14020108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911661PMC
January 2021

Analysis of the immunoglobin E molecular sensitization profile in children with allergic asthma and predictive factors for the efficacy of allergy immunotherapy.

Ann Transl Med 2020 Nov;8(21):1459

Department of Respiratory Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Background: As the incidence of allergic asthma in children increases, the immunoglobin E (IgE) molecular sensitization profile of allergic asthma remains underreported while the level of total IgE (tIgE) and sIgE/tIgE have not been studied as predictors of efficacy of allergen immunotherapy (AIT) for allergic asthma, specifically in children.

Methods: Starting from August 2018 to March 2019 in the Respiratory Department of the Children's Hospital of Chongqing Medical University, asthmatic children, with positive skin prick tests to Der p or Der f, were enrolled in this study. Total IgE, allergen serum-specific IgE (sIgE) of Der p, Der f, (Blo t), cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab, along with Der p allergen components, Der p1 and Der p2, were measured by ImmunoCAP™ assay.

Results: A total of 142 children with allergic asthma were enrolled, all of whom showed positive IgE for Der p, Der p1, Der p2, and Der f; meanwhile, the positive rates of Blo t, cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab were 91.84%, 10.96%, 7.32%, 9.15%, 11.58%, 17.03%, 18.90%, and 18.28% respectively. A significantly high correlation was found between total IgE and the sIgE of Der f, Der p, Der p 1, and Der p 2. Asthmatic children with a family history of allergy displayed higher total IgE and unknown IgE levels than those patients without a family history of allergy. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the negative family history of allergy group than in the positive family history of allergy group. Furthermore, total IgE and unknown IgE were higher in the polysensitized group than in the in monosensitized group. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the monosensitized group than in the polysensitized group.

Conclusions: From this study, we noticed that dust mites are the main cause of asthma in children investigated. Our findings indicate patients with no family history of allergy and monosensitized patients have a higher ratio of sIgE/tIgE, and those patients may benefit more from AIT.
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http://dx.doi.org/10.21037/atm-20-7314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723661PMC
November 2020

Common Variable Immunodeficiency Presenting as Anti-GAD Cerebellar Ataxia.

R I Med J (2013) 2020 Dec 1;103(10):38-39. Epub 2020 Dec 1.

The Warren Alpert Medical School of Brown University, Providence, RI; Department of Neurology, Rhode Island Hospital, Providence, RI.

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December 2020

Formulation and characterization of lornoxicam-loaded cellulosic-microsponge gel for possible applications in arthritis.

Saudi Pharm J 2020 Aug 3;28(8):994-1003. Epub 2020 Jul 3.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan.

Rheumatoid arthritis (RA) is an autoimmune disease associated with severe joint pain. Herein, we report lornoxicam loaded cellulosic microsponge gel formulation with sustained anti-inflammatory effects that are required to manage arthritic pain. The microsponges were formulated using quasi emulsion-solvent diffusion method employing four different surfactant systems, namely polyvinyl alcohol (PVA), Tween80, Gelucire 48/16 and Gelucire 50/13. All the lornoxicam loaded microsponge formulations were extensively characterized with a variety of analytical tools. The optimized microsponge formulation was then converted into gel formulation. The lornoxicam loaded microsponge gel formulation had adequate viscosity and sufficient pharmaceutical properties as confirmed by the texture analysis and the drug release followed Super case II transport. It is noteworthy that we described the preparation of a new cellulosic polymers based microsponge system for delivery of lornoxicam to provide quick as well as lasting (sustained) anti-inflammatory effects in rats using carrageenan induced rat paw edema model. We were able to demonstrate a 72% reduction in inflammation within 4 h using the optimize transdermal gel formulation utilizing Transcutol P as permeation enhancer and with the aid of skin micro-piercing by microneedles, hence, demonstrating the potential of this microsponge gel formulation in arthritis management.
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http://dx.doi.org/10.1016/j.jsps.2020.06.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414098PMC
August 2020

Onychomycosis: Current Understanding and Strategies for Enhancing Drug Delivery into Human Nail Tissue.

Curr Drug Res Rev 2021 ;13(1):25-35

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.

Background: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life.

Objectives: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement.

Conclusion: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.
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http://dx.doi.org/10.2174/2589977512666200731171505DOI Listing
January 2021

A Pathophysiological Perspective on COVID-19's Lethal Complication: From Viremia to Hypersensitivity Pneumonitis-like Immune Dysregulation.

Infect Chemother 2020 Sep 15;52(3):335-344. Epub 2020 Jul 15.

Zymo Research Corporation, Irvine, California, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for our recent coronavirus disease 2019 pandemic, is driving a lung immunopathology that strongly resembles a severe form of hypersensitivity pneumonitis (HP). A review of recent Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV-2 medical reports, as well as described characteristics of HP, lead us to postulate a theory for SARS-CoV-2 severe disease. We propose that the novel SARS-CoV-2 can act as a trigger and substrate of an HP-like severe immune reaction especially in genetically vulnerable individuals in addition to those with immune senescence and dysregulation. Accordingly, the purpose of our letter is to shift the emphasis of concern surrounding immune activity from viral infection to an HP-like severe immune reaction. We review similarities in disease presentation between infection and allergy, relevant immunopathology, and outline phases of SARS-CoV-2 disease with perspectives on therapy and critical care. Altogether, the favored course is to begin treatments that address the disease at the earliest phase before immune dysregulation leading to uncontrolled pulmonary inflammation.
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http://dx.doi.org/10.3947/ic.2020.52.3.335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533209PMC
September 2020

Dose Issues in Cancer Chemotherapy.

Oncology 2020 5;98(8):520-527. Epub 2020 May 5.

Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.

In this review, human methotrexate dosing regimens, as well as their relationship to data from in vitro cell culture and in vivo animal and human studies, are discussed. Low-dose, intermediate-dose, and high-dose therapies are covered. Since in vitro and in vivo screenings of potential cancer drugs are commonplace in the development of cancer chemotherapy, comparisons of the three criteria for effectiveness are important.
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http://dx.doi.org/10.1159/000506705DOI Listing
August 2020

Ictal Catatonia in Autoimmune Encephalitis.

R I Med J (2013) 2020 Apr 1;103(3):55-58. Epub 2020 Apr 1.

Rhode Island Hospital, Brown University, Providence, RI; Morton Hospital, Steward Medical Group, Department of Psychiatry, Taunton, MA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154181PMC
April 2020

Assessing Preoperative Risk Factors With Sex Disparities in Total Joint Arthroplasty Patients and Financial Outcomes From the National Inpatient Sample Database.

J Am Acad Orthop Surg 2020 Nov;28(21):e969-e976

From the Oakland University William Beaumont School of Medicine, (Ms. Cheah) Auburn Hills, MI, Department of Biomedical Sciences, Oakland University William Beaumont School of Medicine, (Dr. Hussein) Auburn Hills, MI, the School of Literature, Sciences and the Arts, University of Michigan, (Mr. A. El Othmani), Ann Arbor, MI, the Division of Kinesiology, Health, and Sport Science, Wayne State University (Mr. Rizvi), and the Department of Orthopaedic Surgery and Sports Medicine, Detroit Medical Center, Detroit, MI (Mr. Rizvi, Dr. Sayeed, Dr. M.M. El-Othmani).

Introduction: Disparities in the healthcare system imply potential risks for vulnerable groups whose needs are not appropriately met. Total joint arthroplasty (TJA) is successful in treating end-stage arthritis, resulting in increased demand for the procedure, however remains underused in both sexes, especially in women. Although multiple studies assessed the differences in postoperative morbidities between sexes, there remains a lack in understanding patients' preoperative clinical profile and nonclinical demographics. The aim of this study is to provide a population-based epidemiologic assessment of preoperative risk factors and sex disparities and assess differences in outcomes following TJA.

Methods: The National Inpatient Sample database from 2006 to 2011 was analyzed. Patients who underwent primary total knee and hip arthroplasty were identified and stratified into two cohorts of male and female, and demographic data and comorbidities were collected. Postoperative complications, length of stay, total charges, and discharge destination were measured for matched cohorts.

Results: Female patients present for TJAs at an older average age, are less likely to present with AIDS, alcohol abuse, coagulopathy, congestive heart failure, drug abuse, liver disease, peripheral vascular disease, and renal failure, and are more likely to present with anemia, autoimmune disorders, chronic obstructive pulmonary disease, depression, obesity, and valvular disease. Postoperatively, the average length of stay for female patients was markedly higher (3.52 versus 3.39) and a lower percentage went home (59% versus 73%). Overall, female patients experience greater odds of any complication while in-patient.

Discussion: This study highlighted sex differences in areas that could account for the underuse of the procedure in both sexes, with women affected to a greater extent. Understanding these factors will help address the unmet needs of both sexes after TJA by encouraging future studies and provider education to ensure that all patients are able to access the necessary procedures for pain relief and functional improvement.
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http://dx.doi.org/10.5435/JAAOS-D-19-00716DOI Listing
November 2020

Vascular malformations masquerading as demyelinating disease.

Mult Scler Relat Disord 2020 Feb 1;38:101410. Epub 2019 Oct 1.

Alpert Medical School of Brown University, 222 Richmond St., Providence, RI, 02906, United States.

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http://dx.doi.org/10.1016/j.msard.2019.101410DOI Listing
February 2020

Acute variceal haemorrhage in the context of posterior flail chest.

ANZ J Surg 2020 04 13;90(4):627-629. Epub 2019 May 13.

School of Medicine, James Cook University, Townsville, Queensland, Australia.

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http://dx.doi.org/10.1111/ans.15271DOI Listing
April 2020

Assessing the effects of post-acute rehabilitation services on health care outcomes for people with multiple sclerosis.

Mult Scler Relat Disord 2019 May 5;30:277-283. Epub 2019 Mar 5.

Department of Health Services, Policy, and Practice and Center for Gerontology and Health Care Research, Brown University School of Public Health, Box G-S121-6, 121 South Main Street, Providence, RI, United States. Electronic address:

Background: The impact of post-acute rehabilitative services provided in skilled nursing facilities (SNF) on a particularly vulnerable, disabled subgroup, namely persons with multiple sclerosis (PwMS), is unknown.

Objective: The objectives of this study were to (1) describe the use of post-acute rehabilitative services in SNFs, and (2) examine the association between the use of physical and occupational therapy (PT/OT) and (a) successful community discharge and (b) functional improvement for PwMS.

Methods: We retrospectively selected PwMS newly admitted to a SNF from the hospital between January 2008 and September 2012. Using the Minimum Data Set (MDS), we examined the receipt of PT/OT and categorized the receipt as high and low intensity PT/OT according to median hours/week. We assessed the association of high vs. low PT/OT with successful discharge to the community and functional improvement using propensity-matched logistic regression.

Results: A total of 26,412 PwMS had valid OT/PT values in the MDS during the study period, among which 24,410 (92.4%) used PT/OT for some time in the SNF. Median PT/OT use was 9.7 h/week. Use of rehabilitation services was higher in patients with less cognitive and functional impairment. Overall, two-thirds (67.3%) of the propensity matched cohorts for Objective 2a (n = 8204/group) were successfully discharged to community; and one-third (33.6%) of the matched cohort for Objective 2b (n = 6803/group) had improved function. Higher PT/OT therapy was associated with successful discharge [odds ratio (OR) 1.20; 95% CI 1.12-1.28] and functional improvement (OR 1.21; 95% CI 1.13-1.30).

Conclusion: PwMS used post-acute rehabilitation services at SNFs for a median of ∼10 h/week. Those who used more rehabilitative services in the post-acute care setting were more likely to be successfully discharged to the community and experience functional improvement after adjustment for major confounders.
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http://dx.doi.org/10.1016/j.msard.2019.03.003DOI Listing
May 2019

Post-menopausal acquired diaphragmatic herniation in the context of endometriosis.

Int J Surg Case Rep 2018 25;53:154-156. Epub 2018 Oct 25.

College of Medicine, James Cook University, Townsville, Queensland, Australia; Surgical Division, Mackay Base Hospital, Mackay, Queensland, Australia.

Introduction: Acquired diaphragmatic hernias are most commonly associated with traumatic thoracic injury and rarely heal spontaneously. Conditions that promote peritoneal seeding, such as endometriosis, are associated with spontaneous acquired diaphragmatic hernia formation. Non-traumatic acquired diaphragmatic herniation has previously been described in the context of catamenial pneumothorax, however post-menopausal endometriotic diaphragmatic herniation has not been previously reported.

Presentation Of Case: A 57 year old post-menopausal female presented with a strangulated ischaemic loop of small bowel herniating through an acquired right sided endometriotic diaphragmatic hernia not previously visualised on imaging. Clamshell thoracolaparotomy was conducted and the necrotic section of small bowel was resected. The diaphragm was repaired and the patient recovered post-operatively without complications.

Discussion: This patient had a complete intestinal malrotation presenting acutely with a small bowel obstruction and herniation through an acquired diaphragmatic rupture. This was possibly related to a diaphragmatic defect caused by endometriosis.

Conclusion: We presented a case of a post-menopausal acquired diaphragmatic herniation secondary to endometriosis; resulting in acute intestinal obstruction and bowel infarction. To our knowledge, such a case has not been previously reported in existing literature.
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http://dx.doi.org/10.1016/j.ijscr.2018.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226825PMC
October 2018

Hashimoto Encephalopathy as a Complication of Autoimmune Thyroiditis.

Med Princ Pract 2019 24;28(1):91-95. Epub 2018 Oct 24.

Palmetto General Hospital, Miami, Florida, USA.

Objective: To present a case of Hashimoto encephalopathy as a complication of autoimmune thyroiditis.

Clinical Presentation And Intervention: A previously healthy 56-year-old female presented with rapidly progressive cognitive decline and visual hallucinations. Being a diagnosis of exclusion, Hashimoto encephalopathy required an extensive laboratory and diagnostic workup, which was done over the course of a 15-day hospitalization. The patient recovered after initial treatment with intravenous methylprednisolone and was then switched to prednisone p.o.

Conclusion: This case report illustrates the importance of awareness for Hashimoto encephalopathy, as it remains one of the few easily treatable and reversible causes of rapid cognitive decline.
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http://dx.doi.org/10.1159/000494800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558315PMC
January 2020

Multiple sclerosis relapse presenting as an acute cardiomyopathy.

Mult Scler Relat Disord 2019 Jan 19;27:7-8. Epub 2018 Sep 19.

Department of Neurology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.

Multiple sclerosis is increasingly being recognized in association with cardiovascular dysfunction, which can manifest with cardiomyopathy, pulmonary edema (Kaplan et al., 2015), orthostasis (Kaplan et al., 2015) and other complications. Takotsubo cardiomyopathy is a syndrome of acute-onset ventricular dysfunction in the absence of obstructive coronary artery disease, which on rare occasion has been observed in the setting of demyelinated plaques in the brainstem. We report on two cases of Takotsubo cardiomyopathy with medullary demyelination secondary to multiple sclerosis.
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http://dx.doi.org/10.1016/j.msard.2018.09.021DOI Listing
January 2019

Rheumatoid Arthritis: A Brief Overview of the Treatment.

Med Princ Pract 2018 2;27(6):501-507. Epub 2018 Sep 2.

Larkin Community Hospital, Miami, Florida, USA.

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease, affecting the joints with varying severity among patients. The risk factors include age, gender, genetics, and environmental exposure (cigarette smoking, air pollutants, and occupational). Many complications can follow, such as permanent joint damage requiring arthroplasty, rheumatoid vasculitis, and Felty syndrome requiring splenectomy if it remains unaddressed. As there is no cure for RA, the treatment goals are to reduce the pain and stop/slow further damage. Here, we present a brief summary of various past and present treatment modalities to address the complications associated with RA.
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http://dx.doi.org/10.1159/000493390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422329PMC
August 2019

Applications of nanoparticle systems in drug delivery technology.

Saudi Pharm J 2018 Jan 25;26(1):64-70. Epub 2017 Oct 25.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Mail Code 6610, P. O. Box 9515, Jeddah 21423, Saudi Arabia.

The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient's compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.
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http://dx.doi.org/10.1016/j.jsps.2017.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783816PMC
January 2018

Influence of polymer ratio and surfactants on controlled drug release from cellulosic microsponges.

Int J Biol Macromol 2018 Apr 14;109:963-970. Epub 2017 Nov 14.

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA.

Microsponge refers to a highly cross-linked particle system with a capacity to adsorb (like a dry sponge) pharmaceutical materials. There are various methods available to prepare microsponge formulations, in this study we used quasi emulsion-solvent diffusion method with a combination of hydrophobic (ethyl cellulose) and hydrophilic (hydroxypropyl methylcellulose) polymers mediated via Tween 80 and polyvinyl alcohol. Various ratios and amounts of the polymers and surfactants were used to prepare microsponge formulations using ketoprofen as a model drug and extensively characterised. Our results, for the first time, indicate successful and optimised formulation with desired pharmaceutical characteristics using a combination of hydrophobic and hydrophilic polymers.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.11.089DOI Listing
April 2018

Protective effect of metoclopramide against organophosphate-induced apoptosis in the murine skin fibroblast L929.

J Appl Toxicol 2018 03 13;38(3):329-340. Epub 2017 Oct 13.

King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia.

This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 μm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 μm) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching ~70-80% protection when they were preincubated at 1 and 5 μm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.
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http://dx.doi.org/10.1002/jat.3543DOI Listing
March 2018

Co-delivery strategies to overcome multidrug resistance in ovarian cancer.

Int J Pharm 2017 Nov 22;533(1):111-124. Epub 2017 Sep 22.

Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan. Electronic address:

Cancer is one of the leading causes of death and equally strikes both genders. Among women, ovarian cancer is responsible for many deaths as it remains symptomless in the earlier stages and generally diagnosed in third stage. At this point it becomes difficult to carry out de-bulking surgery and treatment with different chemotherapeutic drugs has shown resistance, a phenomenon known as multidrug resistance (MDR). Different treatment choices are available for ovarian cancer; however, this article only focuses on various co-delivery strategies, where two different agents are encapsulated in a single carrier and act via different pathways to overcome cancer cell resistance. Ovarian cancer develops MDR via different pathways but majorly involving pump and the non-pump mechanisms in most cases. To overcome MDR it is imperative to strike malignant cells from various directions. Nanocarriers are known to strike the pump mechanism by avoiding the drug efflux pump located on cellular membrane. The efflux pump can also be blocked by blocking activity of ATP binding cassette (ABC) membrane transporters. To stop the non-pump mechanism one can use chemosensitizers, genes, apoptotic factor and others. Treatment of cancer cells could even more effective if the drug is combined with co-agents in a single carrier with targeting moiety. These co-agents along with nanocarriers, allow the drug to accumulate in high enough concentrations in ovarian cancer cells to kill them without affecting normal cells.
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http://dx.doi.org/10.1016/j.ijpharm.2017.09.060DOI Listing
November 2017

Composition, Antioxidant, and Cytotoxic Activities of the Essential Oils from Fresh and Air-Dried Aerial Parts of Pallenis spinosa.

Chem Biodivers 2017 Aug 11;14(8). Epub 2017 Jul 11.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, P.O. Box 926592, Amman, Jordan.

This study was performed to determine the chemical composition, antioxidant and cytotoxic effects of essential oils extracted from the aerial parts of fresh (F-PSEO) and air-dried (D-PSEO) Pallenis spinosa. The composition of the oils was analyzed by gas chromatography (GC) and GC/mass spectrometry, the antioxidant activity by free radical scavenging and metal chelating assays, and their cytotoxicity by a flow cytometry analysis. The primary components in both oils were sesquiterpene hydrocarbons and oxygentated sesquiterpenes. F-PSEO contained 36 different compounds; α-cadinol (16.48%), germacra-1(10),5-diene-3,4-diol (14.45%), γ-cadinene (12.03%), and α-muurolol (9.89%) were the principal components. D-PSEO contained 53 molecules; α-cadinol (19.26%), δ-cadinene (13.93%), α-muurolol (12.88%), and germacra-1(10),5-diene-3,4-diol (8.41%) constituted the highest percentages. Although both oils exhibited a weak radical scavenging and chelating activity, compared to α-tocopherol and ascorbic acid, D-PSEO showed a 2-fold greater antioxidant activity than F-PSEO. Furthermore, low doses of F-PSEO were able to inhibit the growth of leukemic (HL-60, K562, and Jurkat) and solid tumor cells (MCF-7, HepG2, HT-1080, and Caco-2) with an IC range of 0.25 - 0.66 μg/ml and 0.50 - 2.35 μg/ml, respectively. F-PSEO showed a ca. 2 - 3-fold stronger cytotoxicity against the tested cells than D-PSEO. The potent growth inhibitory effect of the plant essential oil encourages further studies to characterize the molecular mechanisms of its cytotoxicity.
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http://dx.doi.org/10.1002/cbdv.201700146DOI Listing
August 2017

Transdermal Bioavailability in Rats of Lidocaine in the Forms of Ionic Liquids, Salts, and Deep Eutectic.

ACS Med Chem Lett 2017 May 12;8(5):498-503. Epub 2017 Apr 12.

Department of Chemistry, The University of Alabama, Tuscaloosa, Alabama 35487, United States.

Tuning the bioavailability of lidocaine was explored by its incorporation into the ionic liquid lidocainium docusate ([Lid][Doc]) and the deep eutectic Lidocaine·Ibuprofen (Lid·Ibu) and comparing the transdermal absorption of these with the crystalline salt lidocainium chloride ([Lid]Cl). Each form of lidocaine was dissolved in a vehicle cream and topically applied to Sprague-Dawley rats. The concentrations of the active pharmaceutical ingredients (APIs) in blood plasma were monitored over time as an indication of systemic absorption. The concentration of lidocaine in plasma varied between applied API-based creams, with faster and higher systemic absorption of the hydrogen bonded deep eutectic Lid·Ibu than the absorption of the salts [Lid]Cl or [Lid][Doc]. Interestingly, a differential transdermal absorption was observed between lidocaine and ibuprofen when Lid·Ibu was applied, possibly indicating different interactions with the tissue components.
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http://dx.doi.org/10.1021/acsmedchemlett.6b00504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430390PMC
May 2017

The 2-μm plasmid encoded protein Raf1 regulates both stability and copy number of the plasmid by blocking the formation of the Rep1-Rep2 repressor complex.

Nucleic Acids Res 2017 Jul;45(12):7167-7179

Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Powai, Mumbai 400076, Maharashtra, India.

The 2-μm plasmid of the budding yeast Saccharomyces cerevisiae achieves a high chromosome-like stability with the help of four plasmid-encoded (Rep1, Rep2, Raf1 and Flp) and several host-encoded proteins. Rep1 and Rep2 and the DNA locus STB form the partitioning system ensuring equal segregation of the plasmid. The Flp recombinase and its target sites FRTs form the amplification system which is responsible for the steady state plasmid copy number. In this work we show that the absence of Raf1 can affect both the plasmid stability and the steady sate copy number. We also show that the Rep proteins do bind to the promoter regions of the 2-μm encoded genes, as predicted by earlier models and Raf1 indeed blocks the formation of the Rep1-Rep2 repressor complex not by blocking the transcription of the REP1 and REP2 genes but by physically associating with the Rep proteins and negating their interactions. This explains the role of Raf1 in both the partitioning and the amplification systems as the Rep1-Rep2 complex is believed to modulate both these systems. Based on this study, we have provided, from a systems biology perspective, a model for the mechanism of the 2-μm plasmid maintenance.
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http://dx.doi.org/10.1093/nar/gkx316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499539PMC
July 2017

Role of Transcription Factors in Steatohepatitis and Hypertension after Ethanol: The Epicenter of Metabolism.

Biomolecules 2016 06 24;6(3). Epub 2016 Jun 24.

Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, Nova Southeastern University, 3200 S University Drive, Fort Lauderdale, FL 33328, USA.

Chronic alcohol consumption induces multi-organ damage, including alcoholic liver disease (ALD), pancreatitis and hypertension. Ethanol and ethanol metabolic products play a significant role in the manifestation of its toxicity. Ethanol metabolizes to acetaldehyde and produces reduced nicotinamide adenine dinucleotide (NADH) by cytosolic alcohol dehydrogenase. Ethanol metabolism mediated by cytochrome-P450 2E1 causes oxidative stress due to increased production of reactive oxygen species (ROS). Acetaldehyde, increased redox cellular state and ROS activate transcription factors, which in turn activate genes for lipid biosynthesis and offer protection of hepatocytes from alcohol toxicity. Sterol regulatory element binding proteins (SREBPs) and peroxisome proliferator activated-receptors (PPARs) are two key lipogenic transcription factors implicated in the development of fatty liver in alcoholic and non-alcoholic steatohepatitis. SREBP-1 is activated in the livers of chronic ethanol abusers. An increase in ROS activates nuclear factor erythroid-2-related factor-2 (Nrf2) and hypoxia inducible factor (HIF) to provide protection to hepatocytes from ethanol toxicity. Under ethanol exposure, due to increased gut permeability, there is release of gram-negative bacteria-derived lipopolysaccharide (LPS) from intestine causing activation of immune response. In addition, the metabolic product, acetaldehyde, modifies the proteins in hepatocyte, which become antigens inviting auto-immune response. LPS activates macrophages, especially the liver resident macrophages, Kupffer cells. These Kupffer cells and circulating macrophages secrete various cytokines. The level of tumor necrosis factor-α (TNFα), interleukin-1beta (IL-1β), IL-6, IL-8 and IL-12 have been found elevated among chronic alcoholics. In addition to elevation of these cytokines, the peripheral iron (Fe(2+)) is also mobilized. An increased level of hepatic iron has been observed among alcoholics. Increased ROS, IL-1β, acetaldehyde, and increased hepatic iron, all activate nuclear factor-kappa B (NF-κB) transcription factor. Resolution of increased reactive oxygen species requires increased expression of genes responsible for dismutation of increased ROS which is partially achieved by IL-6 mediated activation of signal transducers and activators of transcription 3 (STAT3). In addition to these transcription factors, activator protein-1 may also be activated in hepatocytes due to its association with resolution of increased ROS. These transcription factors are central to alcohol-mediated hepatotoxicity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039415PMC
http://dx.doi.org/10.3390/biom6030029DOI Listing
June 2016

Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial.

PLoS One 2016 10;11(6):e0156965. Epub 2016 Jun 10.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.

Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156965PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902195PMC
July 2017

Cytotoxic activity of the novel heterocyclic compound G-11 is primarily mediated through intrinsic apoptotic pathway.

Apoptosis 2016 07;21(7):873-86

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University (NSU), Fort Lauderdale, FL, 33328, USA.

Natural and chemically synthesized heterocyclic compounds have been explored for their potential use as anticancer agents. We had synthesized non-natural heterocyclic analogs and evaluated their anti-tumor activity by measuring effect on cell proliferation and induction of apoptosis in different cell lines. Previously, we identified a pyrazole-containing compound (G-11) showing cytotoxic effect towards leukemia and lymphoma cell lines. In this study, we further investigated the mechanistic aspects of anticancer properties of G-11 in HL-60 cell line. We demonstrated that cytotoxic effect of G-11 is mediated by caspase-dependent apoptosis. However, the involvement of mitochondrial dysfunction induced by G-11 was independent of caspases. G-11 triggered generation of ROS, caused disruption of mitochondrial transmembrane potential, increased release of cytochrome c to the cytosol, and altered the expression of Bcl-2 and Bax proteins. These results suggest significant involvement of intrinsic apoptotic pathway. This study comprehensively details the possible mechanisms of action of a novel heterocyclic compound which could find its potential use as an anticancer agent.
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http://dx.doi.org/10.1007/s10495-016-1248-zDOI Listing
July 2016

Novel anticancer compound [trifluoromethyl-substituted pyrazole N-nucleoside] inhibits FLT3 activity to induce differentiation in acute myeloid leukemia cells.

Cancer Lett 2016 Jun 23;375(2):199-208. Epub 2016 Feb 23.

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University (NSU), Fort Lauderdale, FL 33328, United States.

Anticancer properties of chemically synthesized compounds have continuously been optimized for better efficacy and selectivity. Derivatives of heterocyclic compounds are well known to have selective antiproliferative effect against many types of cancer. In this study, we investigated the ability of an indigenously synthesized anticancer molecule, G-11 [1-(2",3",4",6"-Tetra-O-acetyl-β-D-glucopyranosyl)-4-(3'-trifluoromethylphenylhydrazono)-3-trifluoromethyl-1,4-dihydropyrazol-5-one], to cause selective cytotoxicity and induce differentiation in the acute myeloid leukemia HL-60 cells. G-11 was able to exert cytotoxic effect on hematological (Jurkat, U937, K562, HL-60, CCRF-SB) and solid tumor (MCF-7, HepG2, HeLa, Caco-2) cell lines, with IC50 values significantly lower than noncancerous cells (HEK-293, BJ and Vero) and normal peripheral blood mononuclear cells. G-11 induced differentiation of HL-60 cells to granulocytes and monocytes/macrophages by inhibiting the activation of FLT3 (CD135 tyrosine kinase). ITD-FLT3 mutation found in many acute myeloid leukemia patients could also be targeted by G-11 as exhibited by its inhibitory effect on MOLM-13 and MV4-11 cell lines. Molecular docking studies suggest the involvement of Leu616, Asp698, Cys694 and Cys828 residues in binding of G-11 to FLT3. The ability of G-11 to cause selective cytotoxicity and induce differentiation in cancer cells could be clinically relevant for therapeutic gains.
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http://dx.doi.org/10.1016/j.canlet.2016.02.028DOI Listing
June 2016
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