bluuebunny/crossref_metadata_2025 huggingface dataset:
Embedded Passive Circuit Elements in Low Temperature Co-Fired Ceramic Substrates for Aerospace Electronics
Authors: Smarra Devin A. , Subramanyam Guru , Chodavarapu Vamsy P. , Gogineni Sivaram P. , Semega Kenneth J. , Behbahani Alireza R.
Published: November 2017

The packaging technology plays a critical role in the development of environmentally robust microelectronic systems. There is great demand for microelectronic systems that can withstand harsh environments and high temperatures in numerous applications including down-hole drilling, geothermal drilling, aerospace, heavy industrial, and automotive industries. In these applications, both sensors and interface electronics could be subjected to temperatures of 200°C and beyond. Standard plastic or epoxy based printed circuit boards are not reliable at these temperatures for long term operation. Packaging techniques such as Low Temperature Co-fired Ceramic (LTCC) offer a versatile and reliable alternative to form electronic substrates. LTCC is a multi-layer packaging system that also provides the ability to embedded passive components, such as resistors and capacitors, and thermal management structures within the substrate. This work evaluates the performance of LTCC embedded passive elements from 25°C to 225°C. A variety of passive component designs are evaluated using theoretical calculations, simulations, and measurements of fabricated test structures.
Enantioselective Gas Chromatographic Separation of Racemic N-alkylated Barbiturates: Application of C11-Chirasil-Dex as Chiral Stationary Phase in GC
Authors: Ghanem Ashraf
Published: November 2017

Chirasil-β-Dex containing an undecamethylene spacer (C11-Chirasil-Dex) was synthesized and used as chiral stationary phase (CSP) in enantioselective gas chromatography (GC). The versatility of the new stationary phase in the simultaneous enantiomeric separation of a set of N-alkylated barbiturates is demonstrated.
A Practical Approach to Red Blood Cell Folate Analysis
Authors: Piyathilake Chandrika J , Robinson Constance B , Cornwell Phillip
Published: November 2017

The measurement of folate in red blood cells (RBCs) is preferred since it reflects long-term folate status in the body compared to plasma/serum folate which may be influenced by recent dietary intake. The commonly accepted technique for RBC folate analysis involves preparation of a hemolysate using a fresh whole blood sample. Hematocrit and plasma folate concentrations are needed to calculate RBC folate values. Because of the need for immediate access to a laboratory where processing can be performed, it may not be practical to assess RBC folate status using this method in field-based epidemiological studies. It is however, feasible to isolate packed RBSs from a blood sample under these conditions. The purpose of this study is to validate RBC folate analysis using packed red cells by comparing the RBC folate values obtained by hemolysate method (routine assay) with those obtained by using packed RBCs (new assay) in the same individuals (n = 50) using the folate microbiological assay. The correlation between plasma folate and the routine RBC folate assay (r = 0.58, p = 0.001) and the correlation between plasma folate and the new RBC folate assay was statistically significant (r = 0.55, p = 0.001). The correlation between RBC folate by the routine assay and new assay was also statistically significant (r = 0.78, p < 0.001). We conclude that measurement of folate in packed RBC is a practical approach in assessing long-term folate status in field-based and or larger scale epidemiological studies where an immediate access to a laboratory is unavailable for necessary sample processing for the routine RBC folate assay.
New Spectrofluorimetric Method with Enhanced Sensitivity for Determination of Paroxetine in Dosage Forms and Plasma
Authors: Darwish Ibrahim A. , Amer Sawsan M. , Abdine Heba H. , Al-Rayes Lama I.
Published: November 2017

New simple spectrofluorimetric method with enhanced sensitivity has been developed and validated for the determination of the antidepressant paroxetine (PXT) in its dosage forms and plasma. The method was based on nucleophilic substitution reaction of PXT with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole in an alkaline medium (pH 8) to form a highly fluorescent derivative that was measured at 545 nm after excitation at 490 nm. The factors affecting the reaction was carefully studied and optimized. The kinetics of the reaction was investigated, and the reaction mechanism was presented. Under the optimized conditions, linear relationship with good correlation coefficient (0.9993) was found between the fluorescence intensity and PXT concentration in the range of 80-800 ng ml-1. The limits of detection and quantitation for the method were 25 and 77 ng ml-1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 3%. The proposed method was successfully applied to the determination of PXT in its pharmaceutical tablets with good accuracy; the recovery values were 100.2 ± 1.61%. The results obtained by the proposed method were comparable with those obtained by the official method. The proposed method is superior to the previously reported spectrofluorimetric method for determination of PXT in terms of its higher sensitivity and wider linear range. The high sensitivity of the method allowed its successful application to the analysis of PXT in spiked human plasma. The proposed method is practical and valuable for its routine application in quality control and clinical laboratories for analysis of PXT.
Micellar Electrokinetic Chromatographic Study of the Separation of an Aromatase Inhibitor and a Tryciclic Antidepressant in the Breast Cancer Treatment
Authors: Flores J. Rodríguez , Salcedo A.M. Contento , Fernández L. Muñoz
Published: November 2017

Micellar electrokinetic chromatography (MEKC) was investigated for the simultaneous determination of letrozole, imipramine and their metabolites in human urine samples over a concentration range of therapeutic interest. Experimental parameters such as pH of the running electrolyte, sodium dodecylsulphate (SDS) concentration, borate concentration, voltage, etc were investigated. Under optimal conditions of 25 mM SDS, 15 mM borate buffer (pH 9.2), 15% 2-propanol, as background electrolyte; 28 kV and 40 °C, as voltage and cartridge temperature, respectively; resolution between the peaks was greater than 1.7. Before the determination, a solid phase extraction (SPE) procedure with a C18 cartridge was optimized. Good linearity, accuracy, precision, robustness and ruggedness were achieved and detection limits of 12.5 ng/mL for letrozole and its metabolite and 37.5 ng/mL, were obtained for imipramine and their metabolites. Real determinations of these analytes in two patient urines were carried out. Sensitivity achieved in this method is sufficient to perform kinetic studies in humans.
Development and Validation of a HPLC Method to Determine Griseofulvin in Rat Plasma: Application to Pharmacokinetic Studies
Authors: Wei Bo , Liang Dong , Bates Theodore R.
Published: November 2017

A simple, specific, sensitive, and rapid high performance liquid chromatography (HPLC) method for the determination of griseofulvin in small volumes of rat plasma was developed and validated using warfarin as an internal standard. Biological sample preparation involved simple extraction with acetonitrile, followed by dilution with aqueous mobile phase buffer (20 mM sodium dihydrogen phosphate, pH 3.5) to eliminate any chromatographic solvent effects. Griseofulvin and warfarin were baseline separated and quantitated on a C18 reversed phase column (4.6 x 150 mm, 3.5 µm), using a mobile phase composed of a 20 mM aqueous solution of sodium dihydrogen phosphate-acetonitrile (55:45, v/v, pH 3.5) delivered at a flow rate of 1.0 mL/min, and with fluorescence detection (λexcitation = 300 nm, λemission = 418 nm). The method was proven to be linear over a plasma griseofulvin concentration range of 10 to 2500 ng/mL with a mean correlation coefficient of 0.9996. The intra-day and inter-day accuracy (relative error) were in the range of 0.89% to 9.26% and 0.71% to 7.68%, respectively. The within-day precision (coefficient of variation) was less than 3.0% and the between-day precision was less than 7.5%. The mean recovery of griseofulvin from rat plasma was found to be 99.2%. The limit of detection (LOD) and the limit of quantification (LOQ) of griseofulvin were determined to be 1 ng/mL and 10 ng/mL, respectively. The developed method was successfully applied to quantitatively assess the pharmacokinetics of griseofulvin in rats following a single 50 mg/kg oral dose of the drug.
Pharmacotherapy of HIV: A Focus on Atazanavir/Ritonavir a Potent and Convenient Once Daily Ritonavir Boosted Protease-Inhibitor for HIV-1 Infected Adults
Authors: Allavena Clotilde , Trancart Stéphanie , Cuzin Lise
Published: November 2017

Atazanavir is the first azapeptide protease inhibitor. As a consequence of metabolism by the Cytochrome P450 system and excretion by drug-transporters such as P-Glycoprotein, drug interactions are considerable. They can be used to improve efficacy (ritonavir boosting) but may also cause adverse effects. Efficacy of ATV/RTV has been shown to be comparable to lopinavir/ritonavir in antiretroviral naïve patients, providing even better results in patients with high viral load. Efficacy has also been demonstrated in maintenance therapy in antiretroviral-experienced patients, and in patients with previous virologic failure, providing the best virologic response when the virus harbors less than four resistance PI mutations. The gastrointestinal tolerability and the lipid profile are better than with other PIs. The major side effect is a jaundice caused by unconjugated hyperbilirubinemia that rarely leads to discontinuation. ATV/RTV simple administration as well as tolerability may be linked with better treatment adherence. ATV/RTV is simple, potent and well tolerated. Thus it takes an important place in the treatment of HIV-infected patients, preferentially in antiretroviral-naïve or moderately pretreated populations.
Pharmacotherapy of Bone Loss in Postmenopausal Women: Focus on Denosumab
Authors: Roman-Gonzalez Alejandro , Ackerman Kathryn E.
Published: November 2017

Denosumab is a human monoclonal antibody against RANKL. This antibody decreases bone turnover markers and increases bone mineral density (BMD) in postmenopausal women. In phase 3 studies including more than 1100 women, denosumab achieved greater increases in lumbar spine, total hip, distal 1/3 radius, and total BMD than alendronate 70 mg weekly. Recent data suggest that denosumab also decreases vertebral and non-vertebral fractures. This drug seems to be safe, although the most frequent side effects are arthralgia, back pain, and nasopharyngitis. No increased incidence of neoplasia has been found compared to placebo or alendronate. However, infections requiring inpatient treatment were more frequent in study groups treated with denosumab. These were common community acquired infections and were treated with standard antibiotics. No opportunistic infections were reported. Denosumab is a very promising new drug for the treatment of osteopenia and osteoporosis, and hopefully more long-term safety information and further fracture data will support its commercial use in the near future.
Azacitidine: A Review of its Use in the Management of Myelodysplastic Syndromes
Authors: Lammers Philip E. , Cashen Amanda F.
Published: November 2017

Myelodysplastic syndromes (MDS) are marked by progressive cytopenias and risk of transformation to acute myeloid leukemia. Supportive care with transfusions, antibiotics, and hematopoietic growth factors has long been the mainstay of therapy for MDS, given that most patients are not eligible for more intensive chemotherapy. The hypomethylating agent 5-azacitidine (AZA) was the first chemotherapeutic agent approved by the U.S. Food and Drug Administration for the treatment of MDS, and it represented a real advance in the management of the disease. In Phase III trials, azacitidine demonstrated a higher response rate and a longer overall survival compared to supportive care alone. Importantly, it is a well-tolerated drug that can be given IV or SC in various outpatient schedules. Future studies are expected to evaluate the activity of AZA in combination with other epigenetic modifying agents and to establish the relative efficacy of azacitidine and decitabine. This review summarizes the current treatment landscape in MDS and specifically addresses the role of azacitidine in the management of MDS.
Clopidogrel Bisulfate: A Review of its Use in the Management of Acute Coronary Syndrome
Authors: Rossini Roberta , Musumeci Giuseppe , Nijaradze Tamar , Gavazzi Antonello
Published: November 2017

Antiplatelet therapy is the cornerstone in the modern therapy of patients with acute coronary syndromes (ACS), because of the unique role of platelets in coronary thrombosis. Clopidogrel in combination with aspirin is the current “gold standard” for reducing cardiovascular events in such patients, providing a synergistic platelet inhibition through different platelet activation pathways. Clopidogrel is a thienopyridine which inhibits ADP-induced platelet aggregation, with no direct effects on the metabolism of arachidonic acid. Due to a better safety profile with a similar antiplatelet effectiveness, it is preferred to ticlopidine. In patients with ACS without ST segment elevation (NSTEMI), clopidogrel plus aspirin is able to reduce the relative risk of adverse cardiovascular events by 20%, compared with aspirin alone. Clopidogrel plays a key role also in patients undergoing coronary stenting, in order to prevent stent thrombosis. Pretreatment and long-term treatment with clopidogrel reduces by about one-third the risk of cardiovascular death or myocardial infarction in NSTEMI ACS patients undergoing percutaneous coronary angioplasty (PCI). However, a long-term dual antiplatelet therapy is associated with a higher rate of bleeding events. Clinical practice guidelines currently recommend long-term dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS and a pre-treatment with clopidogrel in every patient scheduled for PCI. The concept of clopidogrel resistance and the need for a pretreatment in patients undergoing coronary stent implantation led to the concept that an improved antiplatelet regimen with novel drugs is desirable.
Hypertension Management and End Organ Protection: Focus on Aliskiren
Authors: Imanishi Toshio , Tsujioka Hiroto , Akasaka Takashi
Published: November 2017

The renin-angiotensin system (RAS) activity is a key factor in the pathophysiology and development of hypertension, atherosclerosis, heart failure, and renal disease. It is unclear whether angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) have fully delivered the expected reductions in cardiovascular risk. In fact, the optimized RAS suppression is difficult to achieve with these agents, partly because ACE inhibitors and ARBs both activate compensatory feedback mechanisms that result in renin release and increase plasma renin activity (PRA). Molecular modeling was used to develop aliskiren, a potent, low-molecular-weight, nonpeptide, direct renin inhibitor with sufficient bioavailability to produce sustained suppression of PRA after oral administration. This report discusses the mechanisms of action of oral renin inhibitors and their pharmacokinetic properties. In addition, the report also evaluates the available data regarding the effects of the renin inhibitor aliskiren in the treatment of hypertension and related cardiovascular disorders.
Pharmacotherapy of Excessive Sleepiness: Focus on Armodafinil
Authors: Russo Michael
Published: November 2017

Excessive sleepiness (ES) is responsible for significant morbidity and mortality due to its association with cardiovascular disease, cognitive impairment, and occupational and transport accidents. ES is also detrimental to patients’ quality of life, as it affects work and academic performance, social interactions, and personal relationships. Armodafinil is the R-enantiomer of the established wakefulness-promoting agent modafinil, which is a racemic mixture of both the R- and S-enantiomers. R-modafinil has a longer half-life and is present at higher circulating concentrations than the S-enantiomer following chronic administration of modafinil and may therefore be the enantiomer predominantly responsible for the beneficial effects of the racemic compound. Armodafinil has been approved by the Food and Drug Administration for the improvement of ES associated with narcolepsy, shift-work disorder, and obstructive sleep apnea following a program of randomized, placebo-controlled clinical trials. This comprehensive medication review discusses the pharmacologic profile of armodafinil and the current evidence regarding its efficacy, safety, and tolerability; appraises patient-reported outcomes data; and suggests additional indications in which armodafinil may be of use.
Glimepiride-pioglitazone Hydrochloride in the Treatment of Type 2 Diabetes
Authors: Derosa Giuseppe , Salvadeo Sibilla Anna Teresa
Published: November 2017

The purpose of this article is to review the effectiveness and tolerability of pioglitazone and glimepiride combination treatment for type 2 diabetes, particularly in the context of metabolic control and cardiovascular prevention. We reviewed studies of pioglitazone and glimepiride combination treatment through literature in the internet based Medline. The search was conducted using the search terms pioglitazone, glimepiride, glycemic control, combination therapy, and type 2 diabetes mellitus. The current evidence shows that pioglitazone in association with glimepiride is an effective option in the treatment of type 2 diabetes. Fixed dose combination permits a better compliance to therapy in patients with type 2 diabetes. More studies are needed to establish a role of pioglitazone and glimepiride in atherosclerosis and cardiovascular prevention beyond glycemic control.
Pharmacotherapy of Mixed Hyperlipidemia with Ezetimibe-Fenofibrate Combination Therapy
Authors: Farnier Michel
Published: November 2017

Mixed hyperlipidemia is a frequent atherogenic dyslipidemia characterized by elevated triglycerides, low HDL cholesterol levels, and excess of small, dense LDL particles, often with elevated apolipoproteinB and non-HDL cholesterol concentrations. Although statins are the drug of first choice, many high-risk patients with mixed hyperlipidemia do not achieve the recommended goals with statin monotherapy. Due to the complementary effects of ezetimibe and fenofibrate on the components of atherogenic dyslipidemia, the combination of these two drugs is an alternative treatment option for patients with mixed hyperlipidemia. However, the potential benefit of ezetimibe-fenofibrate combination therapy in cardiovascular risk reduction strategies remains to be established and this combination therapy should only be considered as a second-line therapy and appears to be particularly useful for patients with a poor response or an intolerance to statin monotherapy.
Reduction in Risk of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes. Focus on Rampiril
Authors: Khazaei M. , Sharifi AM. , Golbidi S. , Laher I.
Published: November 2017

Several clinical studies demonstrate a beneficial role of angiotensin-converting enzyme (ACE) inhibitors in patients with myocardial infarction, hypertension and diabetes mellitus. This review focuses on the effects of ramipril, a weak inhibitor of ACE that is rapidly hydrolyzed to ramiprilat, an active metabolite. The Heart Outcome Prevention Evaluation (HOPE) study evaluated the effects of ramipril in patients with a high risk for cardiovascular events without pre-existing left ventricular dysfunction or heart failure. In this review, we summarized the effects of ramipril on myocardial infarction, death, diabetes mellitus, and stroke.
Safety and Efficacy of I(131) Tositumomab in the Treatment of non-Hodgkin's Lymphoma
Authors: Illidge Tim , Ivanov Andrei , Du Yong
Published: November 2017

B1 or Tositumomab was the first B-cell specific antibody to be discovered and it targets the CD20 antigen. The potential therapeutic importance of this discovery in targeting CD20, however remained unrealised until the mid 1990's when Tositumomab was radiolabelled and the 131I Tositumomab radioimmunotherapy (RIT) regimen (Bexxar™) developed. The 131I Tositumomab regimen is completed within one to two weeks and consists of a tracer dose of the radioimmunoconjugate followed by the therapeutic dose 7 to 14 days later. Each infusion of 131I-tositumomab is preceded by an infusion of a pre-dose of 450 mg “cold” or unlabeled tositumomab. 131I Tositumomab has demonstrated remarkable clinical activity in patients with relapsed follicular lymphoma with high response rates and durable remission even in patients with disease that is refractory to chemotherapy and rituximab antibody therapy. Recent new data has provided new insights into the potential mechanisms of the antibody and targeted radiation effects and these as well as the safety and efficacy of this novel therapy in follicular lymphoma are reviewed.
Cevimeline for the treatment of dry mouth in patients with Sjogren's syndrome
Authors: Coaccioli Stefano , Landucci Priscilla
Published: November 2017

Sjogren's Syndrome (SS) is a chronic autoimmune disease characterized by the presence of xerostomia and xerophthalmia and by the dysfunction of salivary and lacrimal glands. The disease is frequently associated with other systemic manifestations, including vasculitis, pulmonary interstitial disorders and lymphoma. SS constitutes the primary cause of disability and xerostomia can represent an obstacle to deglutition and to oral hygiene, making it difficult for these patients to talk, eat, and swallow. In addition, it can cause tooth decay and recurring candidosis of the oral cavity, as well as premature teeth loss. The treatment of SS is based on the use of artificial tears, saliva substitutes, and lubricants to control the symptoms, and is usually associated with muscarinic agonist drugs such as pilocarpine, especially in cases of severe dryness. Pilocarpine has been proven to increase the secretion of saliva, but its use in clinical practices is highly limited to the short duration of its action, less than 3 hours, which considerably reduces its compliance. There have recently been studies of a new muscarinic receptor agonist, Cevimeline, which has a longer half-life than Pilocarpine (about 5 hours), and has already been commercialised in some countries. The purpose of this article is to review the published literature regarding the pharmacological and clinical properties of this drug, as well as its efficacy, tolerability, and safety in the treatment of xerostomia in patients suffering from primary and secondary SS.
Pharmacotherapy of Chronic Hepatitis B with Entecavir
Authors: Palumbo Emilio
Published: November 2017

Actually three nucleotide/nucleoside analogues are used for chronic hepatitis B: lamivudine, adefovir dipivoxil, entecavir and telbivudine. Lamivudine and adefovir are advantageous for oral administration and safety, but they induce a sustained response after withdrawal of therapy in only a minority of patients. Telbivudine is a new drug and further studies are need to evaluate its real efficacy. Entecavir, a cyclopentyl guanosine analog, is a potent inhibitor of HBV-DNA polymerase and it inhibits both priming and elongation steps of viral DNA replication. In phase II and III clinical trials, entecavir was found to be superior to lamivudine for all primary endpoints evaluated in both nucleoside-naive and lamivudine-resistant patients and it was effective in both HBeAg-positive and HBeAg-negative nucleoside-naive patients. Only one trial has evidenced cases of viral resistance to entecavir. The approved dosage in treatment-naive patients is 0.5 mg/day orally, while in patients who have failed lamivudine therapy or are known to harbour lamivudine-resistant mutants, the approved dosage is 1.0 mg/day.
Emerging Therapies for the Treatment of Essential Tremor
Authors: Shill Holly A.
Published: November 2017

This article will review newer therapies for the treatment of essential tremor as well as cover potential therapies still in development. Drug pharmacology, specific dosing for ET and adverse effects will be reviewed. Finally, a rationale approach to treatment of ET will be discussed.
Hypertension: Focus on Olmesartan Medoxomil
Authors: Bell Allison M. , Nykamp Diane
Published: November 2017

Hypertension is the leading cause of stroke, heart failure, and ischemic heart disease. One of the key regulators of blood pressure is the renin-angiotensin aldosterone system (RAAS). Olmesartan medoxomil, an angiotensin receptor blocker (ARB), counteracts some of the primary effects of the RAAS by selectively and irreversibly binding to the type 1 angiotensin II receptor (AT1-R). The pharmacokinetic profile of this ARB allows for the convenience of one a day dosing. The pharmacodynamic profile of olmesartan is favorable because it is neither metabolized by, induces, nor inhibits the CYP450 isozyme system. The metabolism of the prodrug to the active form occurs in the gut by the enzyme arylesterase. No further metabolism and a lack of interaction with the CYP450 isozyme system leads to very few drug interactions with olmesartan medoxomil.

Numerous studies have been conducted to evaluate the efficacy, safety, and tolerability of olmesartan medoxomil. Studies have been conducted to compare olmesartan medoxomil to other angiotensin receptor blockers. The efficacy of olmesartan medoxomil has been compared to other classes of antihypertensive agents. Results of all trials have proven non-inferiority of olmesartan medoxomil to other antihypertensive agents; some studies have shown superior blood pressure control provided by olmesartan medoxomil when starting dosages are evaluated. Overall, olmesartan medoxomil has the potential to facilitate the achievement of blood pressure goals, enhance compliance with a once daily dosing regimen, and is associated with minimal side effects. Olmesartan medoxomil has been proven to be a safe and effective antihypertensive drug when compared to other ARBs and other antihypertensive agents.
Pegylated Liposomal Doxorubicin for Advanced Ovarian Cancer in Women who are Refractory to Both Platinum- and Paclitaxel-Based Chemotherapy Regimens
Authors: Sugiyama Toru , Kumagai Seisuke
Published: November 2017

Pegylated liposomal doxorubicin (PLD) is doxorubicin HCl encapsulated in long-circulating STEALTH® liposomes (Doxil®). PLD achieves good response rates and many patients maintain long-lasting stable disease (SD), which is one of the advantages. In addition, the clinical benefit is high in platinum-resistant disease, and PLD is thus considered to be the first option. PLD is associated with a number of adverse events, but these events are mild to moderate. PLD is safer for heavily pretreated patients than topotecan and gemcitabine due to mild bone-marrow toxicity, but that nonhematotoxity, such as PPE, stomatitis, mucositis, and other cutaneous reactions were the most common side effects attributable to PLD. Based on a review of previous studies, there are no differences in efficacy between 50 and 40 mg/m2 of PLD, therefore, a dose of 40 mg/m2 is preferable in patients with platinum-resistant disease to reduce adverse events. The 1-hour infusion schedule every 4 weeks makes PLD easy to administer. A rational approach to combine PLD with other drugs should take the slow accumulation and delayed peak of PLD in tumors into consideration. When combined with other useful agents, the lower dose of PLD (30 to 35 mg/m2) with a 3-week schedule may reduce severe PPE and stomatitis with negligible effects on the level of DI and the therapeutic efficacy.
A Review of Delayed-Release MMX Mesalamine: It's Use in the Treatment of Ulcerative Colitis
Authors: Sharaiha Reem , Swaminath Arun
Published: November 2017

Ulcerative colitis affects approximately 500,000 people within the U.S. For mild to moderate disease, 5-ASA is considered the first line medication to achieve both induction of remission and maintenance of remission. Since the use of sulfasalazine over 40 years ago, numerous new formulations have been created to minimize side effects and maximize drug delivery to the affected colon. Here, we have detailed the currently available 5-ASA formulations and explain why there is room for new and improved 5-ASA formulations. In addition, we will summarize the latest trials detailing the use of MMX mesalamine and where it may fit into the treatment algorithm for our patients with mild to moderate ulcerative colitis.
Pharmacotherapy of Retinal Diseases with Ranibizumab
Authors: Kiernan Daniel F. , Lin Theodore K. , Sheth Veeral , Jager Rama D.
Published: November 2017

The development of new, abnormal and leaky blood vessels, termed choroidal neovascularization, causes loss of vision and quality of life as a result of many ocular diseases. A current therapy for a leading cause of irreversible blindness in older people in the United States, age-related macular degeneration, is intravitreal injection of ranibizumab. However, ranibizumab has also been used off-label to successfully treat a number of other ocular diseases causing significant ocular morbidity, including retinal vascular occlusion and diabetic macular edema. Despite its efficacy, the association of detectable serum levels of ranibizumab and arterial thromboembolic events in major follow-up studies since its approval by the United States Food and Drug Administration as well as its high cost relative to the possible existence of cheaper, equally efficacious alternatives has underscored the importance of understanding the mode of action and clinical utility of this novel pharmacotherapy.
Calcitriol in the Management of Moderate to Severe Plaque Psoriasis
Authors: Saraceno Rosita , Faleri Sara , Chimenti Sergio
Published: November 2017

Psoriasis is a chronic inflammatory cell-mediated disease affecting skin and joints, histologically characterized by epidermal hyperplasia and abnormal differentiation of keratinocytes. Plaque psoriasis, which is the most prevalent form of the disease, is clinically characterized by raised, inflamed, erythematous lesions covered by white silvery scales, located on the elbows, knees, scalp, lower back, forearms, hands and feet. Several drugs are available for the management of moderate-to-severe plaque psoriasis, including topical and systemic treatments. Calcitriol (1,25 dihydroxyvitamin D3) is the most biologically active form of vitamin D3 and it can be used topically as both a primary and adjunctive therapy for psoriasis. Based on evidence that calcitriol inhibits proliferation and induces differentiation of epidermal cells, this hormone has been used successfully in the treatment of psoriasis. This article reviews the effectiveness and safety of calcitriol for the treatment of patients with psoriasis and recent findings related with the mechanism of action.
Pharmacotherapy of HIV: Focus on Etravirine
Authors: Lapadula Giuseppe , Soria Alessandro , Gori Andrea
Published: November 2017

Etravirine (ETR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) designed for binding to HIV reverse transcriptase in spite of most of the mutations which normally confer resistance to the other drugs of the same class. Evidences from clinical trials and post-marketing drug use provide guidance for the use of the drug in NNRTI-experienced patients. However, despite the raised genetic barrier, progressive loss of ETR susceptibility is seen as resistance mutations accumulate and a certain degree of cross-resistance with first-generation NNRTI occurs however. Moreover, most of the experiences in using ETR come from the setting of co-administration with darunavir/ritonavir, whilst little is known about its use with other companions. A full knowledge of all available evidences on the drug is therefore needed, in order to optimize the use of ETR in clinical practice.
Cinacalcet HCl Treatment in Patients with Chronic Kidney Disease Stage 3-4
Authors: Tominaga Yoshihiro
Published: November 2017

It has been clarified in patients with CKD stage 3-4, cinacalcet can reduce PTH levels without severe adverse events, however calcium levels significantly decrease and phosphorus levels increase. Increase of serum phosphorus level by cinacalcet in patients with CKD stage 3-4 is a problematic issue. Undesirable decreases in serum calcium and increases in serum phosphorus caused by cinacalcet require further investigation. For patients with CKD stage 3-4 who suffer from severely advanced 2HPT which cannot be controlled by the usual medical treatment or PTx, cinacalcet can be a useful medication for managing 2HPT.
Treatment of Anemia Associated with Chronic Kidney Disease with Methoxy Polyethylene Glycol-Epoetin Beta
Authors: Patel Tejas , Singh Ajay K.
Published: November 2017

Anemia resulting from a relative deficiency of erythropoietin commonly complicates chronic kidney disease (CKD). With the introduction of recombinant erythropoietin two decades ago, there has been a dramatic reduction in the need for blood transfusions in CKD patients. Epoetin alpha is a first generation erythropoiesis stimulating agent (ESA) that needs to be administered frequently because of its short half-life. Methoxy ethylene glycol-epoetin beta is a longer acting ESA that acts as a continuous erythropoietin receptor activator and is given once every 2 to 4 weeks. In short term clinical studies, Methoxy polyethylene glycol-epoetin beta has been observed to be comparable with other ESAs with regard to safety and efficacy in maintaining hemoglobin levels in the target range. However, hemoglobin is no longer a clinically valid surrogate for safety i.e. correction of anemia does not translate into better clinical outcome. Long term studies evaluating hard end-points such as death and cardiovascular events are lacking. Methoxy polyethylene glycol-epoetin beta has been approved for use in the European Union since 2007 while its use in the United States is prohibited on legal grounds.
Time Course Analysis of Aminoglycoside-Induced Elevation of Serum Creatinine
Authors: Sweileh Waleed M.
Published: November 2017

Objective

The present study aimed to determine the time course of aminoglycoside-induced serum creatinine (SCr) elevation and compare that in patients treated with amikacin (AK) and those treated with gentamicin (GM).

Methodology

A one-year, non-interventional prospective study of patients with normal baseline renal function and were administered either GM or AK. The study was carried out at the internal medicine department of Al-Watani governmental hospital. Outcome of interest was the time course of serum creatinine elevation during the course of aminoglycoside therapy. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS 16).

Results

The study was performed in 94 patients, who had to be administered GM or AK by intravenous injections. In both groups, the significant rise in SCr was detected on the 4th day of therapy. However, GM induced up to 32% increase while AK induced up to 19.5% increase in SCr from baseline levels. In the course of AK treatment, patients on single dosing frequency and those <65 years of age did not show a significant increase in SCr levels during the 6-day therapy. In the course of GM therapy, patients on single frequency dosing, younger patients and females showed a significant elevation in SCr on the 5th day while elderly, males and those on multiple dosing showed a significant elevation on the 4th day of therapy. However, all patient categories on GM therapy showed similar extent of SCr elevation.

Conclusion

In patients with normal renal function, GM and AK showed similar time course but different extent of SCr elevation. Amikacin induced no SCr elevation when given in single dosing frequency or when given to younger patients. Such effects were not observed with GM.
A Review of the Impact of Lapatinib on Health-Related Quality of Life in the Management of Advanced solid Tumors
Authors: Price Julie , Chu Quincy Siu-chung
Published: November 2017

Lapatinib is an oral dual inhibitor of epidermal growth factor receptor (HER1/ErbB1/EGFR) and human epidermal growth factor receptor 2 (HER2/ErbB2) which was approved for use in patients with metastatic breast cancer in 2007. In this review, we discuss the quality of life (QOL) results for patients on clinical trials of lapatinib. Six clinical trials, including 4 phase III and 2 phase II trials, were identified for which QOL outcomes have been reported. The trials generally showed stability of QOL during lapatinib therapy with no trial showing a detrimental effect of lapatinib on QOL. With these results, a discussion of the role of QOL assessments in patients with breast cancer is presented.
Malfunction in GABA and Glutamate as Pathways to Depression: A Review of the Evidence
Authors: Sharpley Christopher F
Published: November 2017

With nearly one fifth of the population experiencing depression sometime during their lives, plus the recent finding that depression rivals smoking in its association with mortality, the search for effective pharmacological treatments for depression remains urgent. However, despite this heavy disease burden upon society, the various waves of antidepressants developed in the last 40 years have shown significant side effects and little specific efficacy over placebo. One potential treatment may be via re-establishment of glutamate and GABA neurotransmitter systems that have been shown to malfunction in depressed patients. The literature describing possible causal links between GABA and/or glutamate malfunction and depression is reviewed, plus those studies which provide experimental data to confirm this hypothesis. While there is plausible support for the links between malfunction of these neurotransmitters and depression, few data exist yet regarding development of effective antidepressant medications based upon these findings.
A Review of Multimatrix System (MMX) Mesalazine in the Management of Ulcerative Colitis
Authors: Hawthorne A Barney
Published: November 2017

MMX™ mesalazine is a novel delayed release mesalazine formulation with a high-strength 1.2 g tablet for the treatment of active mild to moderate colitis and maintenance of remission. In vitro and in vivo studies show initiation of drug release in the terminal ileum and caecum with gradual release of 5-ASA as the tablet passes through the colon. Pharmacokinetic data are comparable to other 5-ASA formulations with low systemic absorption and high levels in feces and in mucosal biopsies in the left colon. Clinical trials have shown high rates of clinical and endoscopic remission in active mild to moderate colitis over 8 weeks with a 2.4 g once daily dose. There do not appear to be higher remission rates with the 4.8 g dose. Prolongation of treatment with a further 8 weeks of 2.4 g twice daily can induce remission in those failing the initial 8 weeks of therapy. A maintenance study enrolling patients who achieved remission in the acute studies showed high rates of remission maintained at one year with 1.2 g twice daily (68.5%) and 2.4 g once daily (64.4%) using the strict definition of remission (including mucosal healing) that was used in the active treatment trials. The drug is safe and effective in colitis. The high tablet strength, and once-daily dosage make this formulation a welcome addition to therapy options for patients with colitis.
Lapatinib in the Treatment of Breast Cancer
Authors: Yamauchi Hideko , LaFortune Tiffany , Ueno Naoto T.
Published: November 2017

Lapatinib is an oral dual tyrosine kinase inhibitor against epidermal growth factor receptor (EGFR) and HER-2/ neu (HER2). The success of trastuzumab in breast cancer prompted investigations of lapatinib in breast cancer, which revealed that lapatinib has effectiveness similar to that of trastuzumab. Clinical trials showed that lapatinib is effective for patients with HER2-positive breast cancer. Furthermore, lapatinib may be effective in patients with central nervous system metastasis that developed after trastuzumab therapy. Lapatinib may have synergistic effects with trastuzumab or hormonal therapy. There are encouraging preliminary data on the efficacy of lapatinib in patients with inflammatory breast cancer. Ongoing trials may give us exciting data on lapatinib as adjuvant therapy. HER2 positivity is a strong predictor of response to lapatinib, but the predictive value of EGFR positivity is less clear. While cardiac toxic effects have been observed with lapatinib, their incidence and severity are less significant than with trastuzumab. Current data indicate that lapatinib is a promising agent with unique potential benefits in the treatment of metastatic breast cancer.
On the Size of an Expression in the Nyman–Beurling-Báez–Duarte Criterion for the Riemann Hypothesis
Authors: Maier Helmut , Rassias Michael Th.
Published: November 2017

A crucial role in the Nyman–Beurling–Báez-Duarte approach to the Riemann Hypothesis is played by the distance

where the infimum is over all Dirichlet polynomials

of length N. In this paper we investigate under the assumption that the Riemann zeta function has four nontrivial zeros off the critical line.
Outcome of Evidence-based Allocation of Single-dose Antibiotic extended to Three-dose Antibiotic Prophylaxis in Surgical Site Infection
Authors: Jogdand Sangita , Shinde Raju , Chandrakar Naman
Published: November 2017

Aim: To study the outcome of evidence-based allocation of single-dose antibiotic extended to three-dose antibiotics prophylaxis in surgical site infection (SSI).

Materials and methods: A total of 183 clean surgical procedures in all age groups and of both genders with encountered comorbidities were included in the study. Surgical procedures like inguinal hernia, primary vaginal hydrocele, congenital hernia and hydrocele, fibroadenoma, and other surface swellings were targeted procedures. These procedures were of <1 hour duration and American Society of Anesthesiologists (ASA) grades I and II in study population. Ceftriaxone with sulbactam 1.5 gm was prophylactic antibiotic given 1 hour prior to incision. Excess local signs for inflammation were observed strictly for extension of antibiotics to three doses or multiple doses.

Results: Success of evidence-based policy of randomization to single or three doses was 76.5% in all patients, and converting to three doses was 85.7%. Favorable outcome was seen in the patients with comorbidities—76.19% in hypertension, 57.14% in diabetes, and 28.57% in obesity. Only 14.3% of overall patients required extended multiple dose antibiotic therapy, which clearly projects that evidence-based policy implementation was effective in reducing number of doses.

Conclusion: Evidence-based flexible antibiotic dose is effective in commonly performed procedures even with comorbidities. Flexibility depending on local signs to modify dose policy gives piece of mind with excellent outcome.

Clinical significance: Adopting flexible antibiotic dosing reduces cost of antibiotics therapy with positive mindset for accepting reduced numbers of doses without affecting the outcome of surgical procedure.
Utility of GeneXpert in Diagnosis of Multidrug-resistant Extrapulmonary Tuberculosis
Authors: Chaudhary Ankush , Utpat Ketaki , Desai Unnati , Joshi Jyotsna
Published: November 2017

Background: The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay (GeneXpert) is a rapid semi-quantitative nucleic acid amplification test with established role in the diagnosis of pulmonary tuberculosis (PTB) and multidrug-resistant (MDR) PTB. We determined the performance of the GeneXpert assay for the diagnosis of extrapulmonary tuberculosis (EPTB) MDR cases.

Aims and objectives: To study the role of GeneXpert in the diagnosis of EPTB MDR.

Materials and methods: A retrospective study was conducted over a period of 2 years at a tertiary care hospital after Ethics Committee permission. Data of 44 consecutive patients of diagnosed EPTB MDR were retrieved for GeneXpert and culture drug susceptibility test (DST). Sensitivity of GeneXpert in the diagnosis of EPTB MDR was calculated comparing culture DST results.

Results: Various EPTB MDR cases studied were lymph node TB (n = 23) 51%, pleural effusion (n = 14) 32%, central nervous system TB/spinal TB/psoas abscess/gluteal abscess (n = 7) 17%. Sensitivity for GeneXpert was found to be 91.30, 57, 100% respectively. True positive and false negative were 36 and 8 cases respectively. The overall sensitivity of GeneXpert in diagnosing EPTB MDR was 81.80%. The sensitivity among lymph node, pleural effusions, and spinal/psoas abscess/gluteal abscess was 91.30, 57.14, and 100% respectively.

Conclusion: GeneXpert sensitivity for the diagnosis of EPTB MDR varied with site of extrapulmonary involvement, with lower sensitivity in pleural fluid as compared with higher sensitivity among lymph node and spine TB. Nevertheless, given the rapid turnaround time and simplicity, it is a useful tool in the diagnosis of EPTB MDR when used in correct clinical context. Subsequent confirmation with culture DST, however, is recommended to diagnose false negatives.
A Study to Compare Antigen-based Enzyme-linked Immunosorbent Assay, Rapid Method, and Microscopy for Detection of Malaria in Blood Donors to prevent Transfusion-transmitted Malaria
Authors: Shrivastava Manisha , Nirankari Priya , Singh Sangita , Navaid Seema
Published: November 2017

Introduction: In malaria-endemic countries, blood donors with low parasitemia may be missed at the time of screening of blood units leading to the consequences like hemolysis, morbidity, and even mortality in nonimmune transfusion recipient. This study aimed to compare peripheral blood smear (microscopy), rapid diagnostic test (RDT), and antigen detection enzyme-linked immune sorbent assay (ELISA) for the detection of Plasmodium spp. in blood donors to prevent transfusion-transmitted malaria (TTM).

Materials and methods: Samples from 100 eligible blood donors coming to donate blood at the Bhopal Memorial Hospital & Research Center blood bank were collected in ethylenediaminetetraacetic acid vial. Light microscopic examination on both thin and thick smears, RDT, and PAN-specific lactate dehydrogenase antigen detection ELISA were performed on the blood samples and the results were compared.

Results: None of the blood smears or samples from the 100 blood donors screened showed malarial parasitemia or positive result.

Conclusion: In India, the current strategy of testing blood donors is mainly restricted to microscopy and some blood banks have adapted rapid methods for antigen detection. A larger study on large sample size should be conducted to determine the most appropriate and effective malarial screening test in blood donors and, most importantly, to suggest a workable national screening policy for prevention of TTM in transfusion recipients.

Clinical significance: For screening blood units for malaria, currently available testing methodologies need to be studied in comparison with the assays with better sensitivity for increasing blood safety and reducing the complications of transmission of malaria to patients through blood transfusions.