ResearchPad - General Pharmacology, Toxicology and Pharmaceutics https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The Impact of Amorphisation and Spheronization Techniques on the Improved in Vitro & in Vivo Performance of Glimepiride Tablets]]> https://www.researchpad.co/product?articleinfo=5b4a54c6463d7e56abaa486e

Purpose: Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique.

Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets.

Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets.

Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo.

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<![CDATA[Process, Physicochemical Characterization and In-Vitro Assessment of Albendazole Microcrystals]]> https://www.researchpad.co/product?articleinfo=5b447f92463d7e3ca3cae938

Purpose: Albendazole is a poorly soluble drug which limits its oral bioavailability. The study was focussed to enhance the solubility by in-situ micronization.

Methods: Albendazole microcrystals were prepared by solvent change method using gum karaya and hupu gum as stabilizing agents and the effect of each stabilizer on the prepared microcrystals were studied. FT-IR, DSC, XRD and SEM analysis were performed as a part of characterization studies. The formulations were evaluated for micromeritics, solubility and drug release. The microcrystals that had shown optimized properties were filled into suitable capsules.

Results: The formulations showed reduction in particle size with uniform size distribution and three folds increase in drug release. The microcrystals had shown more than 100-folds increase in solubility compared to pure drug. Surface energy, enthalpy and crystalline nature of microcrystals were found to be reduced. Microcrystals containing gum karaya had shown more drug release. The filled-in capsules also showed increase in drug release rate. The solubility enhancement of albendazole microcrystals was mainly due to the surface adsorption of the stabilizing agents that led to reduction in surface energy and crystalline nature as substantiated by the DSC and XRD studies. The type of stabilizing agent had significant effect on dissolution rate. High affinity of albendazole with gum karaya led to faster drug release profiles.

Conclusion: The study proved that in-situ micronization is an effective technique to enhance the solubility and dissolution rate of poorly soluble drugs like albendazole.

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<![CDATA[Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells]]> https://www.researchpad.co/product?articleinfo=5b414617463d7e668a65c529

Hematopoiesis is a balance among quiescence, self-renewal, proliferation, and differentiation, which is believed to be firmly adjusted through interactions between hematopoietic stem and progenitor cells (HSPCs) with the microenvironment. This microenvironment is derived from a common progenitor of mesenchymal origin and its signals should be capable of regulating the cellular memory of transcriptional situation and lead to an exchange of stem cell genes expression. Mesenchymal stem cells (MSCs) have self-renewal and differentiation capacity into tissues of mesodermal origin, and these cells can support hematopoiesis through release various molecules that play a crucial role in migration, homing, self-renewal, proliferation, and differentiation of HSPCs. Studies on the effects of MSCs on HSPC differentiation can develop modern solutions in the treatment of patients with hematologic disorders for more effective Bone Marrow (BM) transplantation in the near future. However, considerable challenges remain on realization of how paracrine mechanisms of MSCs act on the target tissues, and how to design a therapeutic regimen with various paracrine factors in order to achieve optimal results for tissue conservation and regeneration. The aim of this review is to characterize and consider the related aspects of the ability of MSCs secretome in protection of hematopoiesis.

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<![CDATA[Standardizing And Democratizing Access To Cancer Molecular Diagnostic Test Data From Patients To Drive Translational Research]]> https://www.researchpad.co/product?articleinfo=5b5a94a3463d7e0ac84de97c

Abstract

In the last 3-5 years, there has been a rapid increase in clinical use of next generation sequencing (NGS) based cancer molecular diagnostic (MolDx) testing to develop better treatment plans with targeted therapies. To truly achieve precision oncology, it is critical to catalog cancer sequence variants from MolDx testing for their clinical relevance along with treatment information and patient outcomes, and to do so in a way that supports large-scale data aggregation and new hypothesis generation. Through the NIH-funded Clinical Genome Resource (ClinGen), in collaboration with NLM’s ClinVar database and >50 academic and industry based cancer research organizations, a Minimal Variant Level Data (MVLD) framework to standardize reporting and interpretation of drug associated alterations was developed. Methodological and technology development to standardize and map MolDx data to the MVLD standard are presented here. Also described is a novel community engagement effort through disease-focused taskforces to provide usecases for technology development.

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<![CDATA[CLINICAL CHARACTERISTICS AND OUTCOME OF PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING AT THE EMERGENCY DEPARTMENT OF A TERTIARY HOSPITAL IN NIGERIA]]> https://www.researchpad.co/product?articleinfo=5afc6145463d7e4a59ae3e9f

Background:

Upper gastrointestinal bleeding is a potentially life threatening condition with multiple causes. There is scarcity of health data depicting the clinical characteristics of the condition in African countries. This study was designed to describe the demographic, clinical characteristics and outcome of the patients who presented to our Emergency Department.

Method:

The records of cohort of all patients admitted with upper gastrointestinal tract bleeding from 1 January 2011 to 31 December 2012 were retrospectively reviewed from admission to discharge or death.

Results:

There were 169 patients with median age of 44.0 years (range 13-89); 25 (15.0%) of them were known peptic ulcer disease patients. Most (69.2%) of the patients were males. The most common presenting symptom was haematemesis (34.9%) followed by melaena (16.6%). There was a history of NSAIDs use in 16.8% and alcohol ingestion in 12%. Upper Gastrointestinal Endoscopy was performed in 6.8% cases. Twenty-three (13.6%) patients died. There was association between mortality and diastolic blood pressure; more deaths (1/7; 14.3%) occurred in those with diastolic blood pressure > 90mmHg compared with ≤90mmHg (5/70; 7.1%) (P = 0.002). There were more deaths among patients who did not receive blood transfusion (4/40; 10.0%) compared with those who had blood transfusion (2/37; 5.4%) (P=0.008).

Conclusion:

The common presentations were haematemesis and melaena, mainly in middle aged men with mortality in one out of seven patients. The high mortality may be due to co-morbidities and poor support services.

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<![CDATA[Aggregated Nanotransfersomal Dry Powder Inhalation of Itraconazole for Pulmonary Drug Delivery]]> https://www.researchpad.co/product?articleinfo=5afbc666463d7e400b9e75c2

Background

Adiponectin and its receptors (AdipoR1 and AdipoR2), known as adiponectin system, have some proven roles in the fat and glucose metabolisms. Several studies have shown that adiponectin can be considered as a candidate in linking metabolism to testicular function. In this regard, we evaluated the correlation between sperm mRNA abundance of adiponectin and its receptors, with sperm motility indices in the present study.

Materials and Methods

In this completely randomized design study, semen samples from 6 adult rams were fractionated on a two layer discontinuous percoll gradient into high and low motile sperm cells, then quantitative parameters of sperm motility were determined by computer-assisted sperm analyzer (CASA). The mRNA abundance levels of Adiponectin, AdipoR1 and AdipoR2 were measured quantitatively using real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the high and low motile groups.

Results

Firstly, we showed that adiponectin and its receptors (AdipoR1 and AdipoR2) were transcriptionally expressed in the ram sperm cells. Using Pfaff based method qRT- PCR, these levels of transcription were significantly higher in the high motile rather than low motile samples. This increase was 3.5, 3.6 and 2.5 fold change rate for Adiponectin, AdipoR1 and AdipoR2, respectively. Some of sperm motility indices [curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR)] were also significantly correlated with Adiponectin and AdipoR1 relative expression. The correlation of AdipoR2 was also significant with the mentioned parameters, although this correlation was not comparable with adiponectin and AdipoR1.

Conclusion

This study revealed the novel association of adiponectin system with sperm motility. The results of our study suggested that adiponectin is one of the possible factors which can be evaluated and studied in male infertility disorders.

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<![CDATA[The Economic Impact of Starting, Stopping, and Restarting an Antibiotic Stewardship Program: A 14-Year Experience]]> https://www.researchpad.co/product?articleinfo=5afa5236463d7e26e07269df

Regions Hospital started a multidisciplinary antibiotic stewardship program (ASP) in 1998. The program effectively shut down from 2002–2004 as key personnel departed and was then restarted but without the dedicated pharmacist and infectious diseases physician. Purchasing data (in dollars or dollars/patient/day) unadjusted for inflation served as a surrogate marker of antibiotic consumption. These data were reviewed monthly, quarterly, and yearly along with antibiotic susceptibility patterns on a semi-annual basis. Segmented regression analysis was use to compare restricted antibiotic purchases for performance periods of 1998–2001 (construction), 2002–2004 (de-construction), and 2005–2011 (reconstruction). After 4 years (1998–2001) of operation, a number of key participants of the ASP departed. For the following three years (2002–2004) the intensity and focus of the program floundered. This trend was averted when the program was revitalized in early 2005. The construction, deconstruction, and reconstruction of our ASP provided a unique opportunity to statistically examine the financial impact of our ASP or lack thereof in the same institution. We demonstrate a significant economic impact during ASP deconstruction and reconstruction.

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<![CDATA[Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2]]> https://www.researchpad.co/product?articleinfo=5af4923c463d7e09b4044727

Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide.

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<![CDATA[Basal Plasma Levels of Copeptin are Elevated in Inactive Inflammatory Bowel Disease after Bowel Resection]]> https://www.researchpad.co/product?articleinfo=5aec3930463d7e3869a1d26d

Evidence of interactions between the enteric nervous system, neuropeptides, and the immune system is growing. The aim of this study was to examine basal plasma levels of a variety of peptide precursors in patients with inflammatory bowel disease (IBD). In two middle-aged cohorts, Malmö Preventive Medicine (n = 5,415) and Malmö Diet and Cost Study (n = 6,103), individuals with the diagnosis of IBD were identified. Medical records were scrutinized. Three controls were matched for each patient. Copeptin, midregional fragments of adrenomedullin, pro-atrial natriuretic peptide, and proenkephalin A, as well as N-terminal protachykinin A and proneurotensin were analyzed in the plasma. Sixty-two IBD patients were identified. The only difference between patients and controls was higher copeptin levels in the patients compared with controls (P = 0.006), with higher copeptin levels in resected than unresected patients (P = 0.020). There was no difference in any precursor levels between Crohn’s disease and ulcerative colitis, between different distributions of disease lesions, or between different treatments.

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<![CDATA[Intraoperative pulseless ventricular tachycardia after Ondansetron]]> https://www.researchpad.co/product?articleinfo=5ad47ec0463d7e353eca6ed1 ]]> <![CDATA[Targeting regulatory T cells in cytokine-induced killer cell cultures (Review)]]> https://www.researchpad.co/product?articleinfo=5ad3f838463d7e2c03475a3a

Regulatory T cells (Tregs) are potent immunosuppressive cells that promote tumor growth and invasion by inducing immune escape and suppressing the antitumor immune response. Cytokine-induced killer (CIK) cells are considered to be the primary candidate for adoptive immunotherapy due to their strong antitumor activity. It was recently reported that the concomitant presence of Tregs may decrease the cytotoxicity of CIK cells. Therefore, depletion or downregulation of Tregs in CIK cell cultures by optimizing the culture program may enhance CIK cell cytotoxicity in vitro and in vivo. The aim of the present review was to summarize the currently available studies on the optimal culture strategy for improving the antitumor activity of CIK cells through targeting Tregs.

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<![CDATA[Hyoscine-N-butylbromide induced ventricular tachycardia during ERCP]]> https://www.researchpad.co/product?articleinfo=5ad28b55463d7e3957cfef05 ]]> <![CDATA[Clinical perspective on statistical equivalence]]> https://www.researchpad.co/product?articleinfo=5acf6db7463d7e1552b3e210 ]]> <![CDATA[Safe intubation in Morquio-Brailsford syndrome: A challenge for the anesthesiologist]]> https://www.researchpad.co/product?articleinfo=5accbe6d463d7e4b5da47264

Morquio-Brailsford syndrome is a type of mucopolysaccharidoses. It is a rare disease with features of short stature, atlantoaxial instability with risk of cord damage, odontoid hypoplasia, pectus carinatum, spine deformities, hepatomegaly, and restrictive lung disease. Neck movements during intubation are associated with the risk of quadriparesis due to cervical instability. This, along with the distortion of the airway anatomy due to deposition of mucopolysaccharides makes airway management arduous. We present our experience in management of difficult airway in a 3-year-old girl with Morquio-Brailsford syndrome posted for magnetic resonance imaging and computerized tomography scan of a suspected unstable cervical spine. As utmost sagacity during intubation is required, the child was intubated inside operation theatre in the presence of experienced anesthesiologists and then shifted to the peripheral location. Intubation was done with an endotracheal tube railroaded over a pediatric fibreoptic bronchoscope passed through the lumen of a classic laryngeal mask airway, keeping head in neutral position.

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<![CDATA[Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late After Myocardial Infarction]]> https://www.researchpad.co/product?articleinfo=5acbccbd463d7e2b3df4859e

In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm3, 42% ± 2% vs. 285 ± 33 mm3, 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm3, P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm3, 4.7% ± 1.9% vs. 1.4 ± 0.4 mm3, 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation.

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<![CDATA[CRLX101 (formerly IT-101) – A Novel Nanopharmaceutical of Camptothecin in Clinical Development]]> https://www.researchpad.co/product?articleinfo=5abd9ee7463d7e73cbae3479

CRLX101 (formerly IT-101) is a first-in-class nanopharmaceutical, currently in Phase 2a development, which has been developed by covalently conjugating camptothecin (CPT) to a linear, cyclodextrin-polyethylene glycol (CD-PEG) co-polymer that self-assembles into nanoparticles. As a nanometer-scale drug carrier system, the cyclodextrin polymeric nanoparticle technology, referred to as “CDP”, has unique design features and capabilities. Specifically, CRLX101 preclinical and clinical data confirm that CDP can address not only solubility, formulation, toxicity, and pharmacokinetic challenges associated with administration of CPT, but more importantly, can impart unique biological properties that enhance CPT pharmacodynamics and efficacy.

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<![CDATA[Comparison of the effect of a single dose of erythromycin with pantoprazole on gastric content volume and acidity in elective general surgery patients]]> https://www.researchpad.co/product?articleinfo=5abc29f6463d7e34c3bc9d8b

Introduction:

Pulmonary aspiration of gastric contents remains one of the most feared complications of anesthesia. A gastric pH of 2.5 or less and a volume of 25 ml (0.4 ml/kg body weight) or more in average adult patients are considered critical factors for the development of pulmonary damage in adults.

Materials and Methods:

This study compared the efficacy of a single oral dose of erythromycin (a macrolide antibiotic) with oral pantoprazole (a proton pump inhibitor) on pre-operative gastric fluid volume and pH in a prospective, randomized, double-blind controlled fashion in 80 adult patients (of ASA physical status I and II) planned for elective surgery under general anesthesia. Patients were divided into two groups of 40 patients each. The pantoprazole group (Group I) received oral pantoprazole 40 mg and the erythromycin group (Group II) received oral erythromycin 250 mg at least 1 h prior to the induction of anesthesia. After tracheal intubation, gastric fluid was aspirated via a Salem Sump tube and its volume and pH were measured.

Results:

Although both erythromycin and pantoprazole decreased the gastric fluid volume to a similar extent, the decrease in gastric fluid acidity by pantoprazole was significantly greater than that by erythromycin. The proportion of patients at risk of pulmonary aspiration according to traditional criteria, i.e. pH ≤2.5 and volume ≥25ml, was lower in the pantoprazole group.

Conclusion:

Administration of pantoprazole was found to be more useful than a sub-therapeutic dose of erythromycin in decreasing both volume and acidity of gastric content.

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<![CDATA[A Pilot Study to Evaluate Pharmaceutical Pictograms in a Multispecialty Hospital at Dehradun]]> https://www.researchpad.co/product?articleinfo=5abbfbe9463d7e2dae269790

Pharmaceutical pictograms have the potential to play an important role in optimizing compliance in the illiterate patient population. Pictograms may improve warning comprehension for those with visual or literacy difficulties and can sometimes be recognized and recalled far better than words. The main purpose of this study is to determine whether these pictograms can be effectively understood by illiterate patients, who otherwise cannot read the instructions given on their prescription order. In this study, 10 pharmaceutical pictograms were evaluated in patients attending the outpatient department of the Shri Mahant Indresh Hospital, a multispecialty, referral hospital in Dehradun (Uttarakhand). Understanding of pictograms by patients before and after interpretation was noted and follow-up interpretation was also noted. Results of the study showed that prior to explanation, the majority of the patients were unable to interpret the pictograms correctly but after explanation of their meaning, interpretation by them showed a marked improvement, indicating the need of using pictograms along with verbal reinforcement. The study also highlighted poor patient follow-up, a major cause of patient non-compliance, often leading to a poor therapeutic outcome of the prescribed medication order. Such problems can be taken care of by an active participation by healthcare professionals.

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<![CDATA[Immigrant background and medicine use for aches: national representative study of adolescents]]> https://www.researchpad.co/product?articleinfo=5989daaaab0ee8fa60ba8eb6

Objectives

The aims of the study were to examine the association between immigrant background and medicine use for headache and stomach-ache among adolescents, and whether symptoms of headache and stomach-ache could explain the differences in medicine use.

Methods

We used data from the Danish contribution to the WHO-affiliated international cross-sectional survey Health Behaviour in School-aged Children (HBSC) in 2006. Among boys, a total of 4170 ethnic Danes, 244 descendants of immigrants, and 224 immigrants participated. Among girls, 4310 ethnic Danes, 264 descendants of immigrants, and 232 immigrants were included. The associations between migrant background and medicine use for headache and stomach-ache by means of multilevel multivariate logistic regression analyses adjusted for age group, symptoms and the clustering effect of school and stratified by sex due to interactions.

Results

Among boys, the risk of medicine use for stomach-ache was higher for immigrants (odds ratio (OR), 1.54; 95% confidence intervals (CI), 0.99-2.44)) and descendants (OR, 1.97 (1.33-2.94)) compared to ethnic Danes. Similar associations were found for use of medicine for stomach-ache for immigrant girls (OR, 1.55 (1.12-2.15) and use of medicine for headache among boys (immigrants (OR, 1.36 (1.02-1.97 and descendants (1.48 (1.12-1.97)). Symptoms of aches were all independently associated with medicine use. After adjusting for these factors the association between immigrant background and medicine use attenuated slightly.

Conclusion

Among adolescents in Denmark, the risk of medicine use for headache and stomach-ache was higher for immigrants and descendants as compared to ethnic Danes, with the exception of medicine use for headache among girls.

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<![CDATA[National medicines policies &#8211; a review of the evolution and development processes]]> https://www.researchpad.co/product?articleinfo=5989dacbab0ee8fa60bb4113

Objectives

Continuous provision of appropriate medicines of assured quality, in adequate quantities, and at reasonable prices is a concern for all national governments. A national medicines policy (NMP) developed in a collaborative fashion identifies strategies needed to meet these objectives and provides a comprehensive framework to develop all components of a national pharmaceutical sector. To meet the health needs of the population, there is a general need for medicine policies based on universal principles, but nevertheless adapted to the national situation. This review aims to provide a quantitative and qualitative (describing the historical development) study of the development process and evolution of NMPs.

Methods

The number of NMPs and their current status has been obtained from the results of the assessment of WHO Level I indicators. The policy formulation process is examined in more detail with case studies from four countries: Sri Lanka, Australia, former Yugoslav Republic of Macedonia and South Africa.

Results

The number of NMPs worldwide has increased in the last 25 years with the highest proportional increase in the last 5–10 years in high-income countries. Higher income countries seem to have more NMP implementation plans available and have updated their NMP more recently. The four case studies show that the development of a NMP is a complex process that is country specific. In addition, it demonstrates that an appropriate political window is needed for the policy to be passed (for South Africa and the FYR Macedonia, a major political event acted as a trigger for initiating the policy development). Policy-making does not stop with the official adoption of a policy but should create mechanisms for implementation and monitoring. The NMPs of the FYR Macedonia and Australia provide indicators for monitoring.

Conclusions

To date, not all countries have a NMP since political pressure by national experts or non-governmental organizations is generally needed to establish a NMP. Case studies in four countries showed that the policy process is just as important as the policy document since the process must create a mechanism by which all stakeholders are brought together and a sense of collective ownership of the final policy may be achieved.

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