bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Plasmid Transformation Method Mediated by Chrysotile, Sliding Friction, and Elastic Body Exposure
Authors: Yoshida Naoto , Nakajima-Kambe Toshiaki , Matsuki Kaori , Shigeno Toshiya
Published: November 2017

Escherichia coli as a plasmid recipient cell was dispersed in a chrysotile colloidal solution, containing chrysotile adsorbed to plasmid DNA (chrysotile-plasmid cell mixture). Following this, the chrysotile-plasmid cell mixture was dropped onto the surface of an elastic body, such as agarose, and treated physically by sliding a polystyrene streak bar over the elastic body to create friction. Plasmid DNA was easily incorporated into E. coli, and antibiotic resistance was conferred by transformation. The transformation efficiency of E. coli cultured in solid medium was greater than that of E. coli cultured in broth. To obtain greater transformation efficiency, we attempted to determine optimal transformation conditions. The following conditions resulted in the greatest transformation efficiency: the recipient cell concentration within the chrysotile-plasmid cell mixture had an optical density greater than or equal to 2 at 550 nm, the vertical reaction force applied to the streak bar was greater than or equal to 40 g, and the rotation speed of the elastic body was greater than or equal to 34 rpm. Under these conditions, we observed a transformation efficiency of 107 per μg plasmid DNA. The advantage of achieving bacterial transformation using the elastic body exposure method is that competent cell preparation of the recipient cell is not required. In addition to E. coli, other Gram negative bacteria are able to acquire plasmid DNA using the elastic body exposure method.
Use of Fourier Transform Infrared (FTIR) Spectroscopy to Study Cadmium-Induced Changes in Padina Tetrastromatica (Hauck)
Authors: D'Souza Lisette , Devi Prabha , Divya Shridhar M.P. , Naik Chandrakant G.
Published: November 2017

The aim of this study is to adopt the approach of metabolic fingerprinting through the use of Fourier Transform Infrared (FTIR) technique to understand changes in the chemical structure in Padina tetrastromatica (Hauck). The marine brown alga under study was grown in two different environmental conditions; in natural seawater ( P. tetrastromatica (c)) and in seawater suplemented with 50 ppm of cadmium ( P. tetrastromatica (t)) for a three-week period in the laboratory. The second derivative, IR specrum in the mid-infrared region (4000-400 cm-1) was used for discriminating and identifying various functional groups present in P. tetrastromatica (c). On exposure to Cd, P. tetrastromatica (t) accumulated 412 ppm of Cd and showed perturbation in the band structure in the mid-IR absorption region. Variation in spectral features of the IR bands of P. tetrastromatica (untreated and treated) suggests that cadmium ions bind to hydroxyl, amino, carbonyl and phosphoryl functionalities. This was attributable to the presence of the following specific bands. A band at 3666 cm-1 in untreated P. tetrastromatica (c) while a band at 3560 cm-1 in Cd-treated P. tetrastromatica (t) due to non bonded and bonded O-H respectively. Similarly, non bonded N-H for P. tetrastromatica (c) showed two bands at 3500 cm-1 and 3450 cm-1 due to the N-H stretching vibrations and a band at 1577cm-1 due to N-H bending vibrations, while an intense band at 3350 cm-1 due to bonded N-H stretching vibrations and at 1571 cm-1 due to bending vibrations was observed for Cd-treated P. tetrastromatica (t). Involvement of ester carbonyl group is characterized by the presence of a band at 1764 cm-1 in untreated P. tetrastromatica (c) while the Cd-treated P. tetrastromatica (t) showed the band at 1760 cm-1. The intensity of the band at 1710 cm-1 in the control samples decreased drastically after cadmium treatment indicating carbonyl of COOH to be involved in metal chelation. A band at 1224 cm-1 for untreated P. tetrastromatica ( c) and at 1220 cm-1 for Cd-treated P. tetrastromatica (t) is indicative of the involvement of phosphoryl group in metal binding. Several other such changes were also evident and discussed in this paper. Based on our observation, FTIR technique proves to be an efficient tool for detecting structural changes and probable binding sites induced by the presence of a metal pollutant, cadmium, in the marine environment.
Optimized and Validated Spectrophotometric Methods for the Determination of Enalapril Maleate in Commercial Dosage Forms
Authors: Rahman Nafisur , Haque Sk Manirul
Published: November 2017

Four simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of enalapril maleate in pharmaceutical formulations. The first method is based on the reaction of carboxylic acid group of enalapril maleate with a mixture of potassium iodate (KIO3) and iodide (KI) to form yellow colored product in aqueous medium at 25 ± 1°C. The reaction is followed spectrophotometrically by measuring the absorbance at 352 nm. The second, third and fourth methods are based on the charge transfer complexation reaction of the drug with p-chloranilic acid (pCA) in 1, 4-dioxan-methanol medium, 2, 3-dichloro 5, 6-dicyano 1, 4-benzoquinone (DDQ) in acetonitrile-1,4 dioxane medium and iodine in acetonitrile-dichloromethane medium. Under optimized experimental conditions, Beer's law is obeyed in the concentration ranges of 2.5-50, 20-560, 5-75 and 10-200 µg mL-1, respectively. All the methods have been applied to the determination of enalapril maleate in pharmaceutical dosage forms. Results of analysis are validated statistically.
A Simple and Selective Spectrophotometric Method for the Determination of Trace Gold in Real, Environmental, Biological, Geological and Soil Samples Using Bis (Salicylaldehyde) Orthophenylenediamine
Authors: Soomro Rubina , Ahmed M. Jamaluddin , Memon Najma , Khan Humaira
Published: November 2017

A simple high sensitive, selective, and rapid spectrophotometric method for the determination of trace gold based on the rapid reaction of gold(III) with bis(salicylaldehyde)orthophenylenediamine (BSOPD) in aqueous and micellar media has been developed. BSOPD reacts with gold(III) in slightly acidic solution to form a 1:1 brownish-yellow complex, which has an maximum absorption peak at 490 nm in both aqueous and micellar media. The most remarkable point of this method is that the molar absorptivities of the gold-BSOPD complex form in the presence of the nonionic TritonX-100 surfactant are almost a 10 times higher than the value observed in the aqueous solution, resulting in an increase in the sensitivity and selectivity of the method. The apparent molar absorptivities were found to be 2.3 x 10 4 L mol-1 cm-1 and 2.5 x 10 5 L mol-1 cm-1 in aqueous and micellar media, respectively. The reaction is instantaneous and the maximum absorbance was obtained after 10 min at 490 nm and remains constant for over 24 h at room temperature. The linear calibration graphs were obtained for 0.1 -30 mg L-1 and 0.01 -30 mg L-1 of gold(III) in aqueous and surfactant media, respectively. The interference from over 50 cations, anions and complexing agents has been studied at 1 mg L-1 of Au(III); most metal ions can be tolerated in considerable amounts in aqueous micellar solutions. The Sandell's sensitivity, the limit of detection and relative standard deviation (n = 9) were found to be 5 ng cm-2, 1 ng mL-1 and 2%, respectively in aqueous micellar solutions. Its sensitivity and selectivity are remarkably higher than that of other reagents in the literature. The proposed method was successfully used in the determination of gold in several standard reference materials (alloys and steels), environmental water samples (potable and polluted), and biological samples (blood and urine), geological, soil and complex synthetic mixtures. The results obtained agree well with those samples analyzed by atomic absorption spectrophotometry (AAS).
Metformin: A Review of Its Use in the Treatment of Type 2 Diabetes
Authors: Papanas N. , Maltezos E.
Published: November 2017

Metformin is now the most widely prescribed oral hypoglycemic agent. This review outlines its use in the treatment of type 2 diabetes. The main mechanisms of action include reduction of appetite and of intestinal carbohydrate absorption, inhibition of hepatic gluconeogenesis, and increased glucose uptake by peripheral tissues. Metformin has been established as the drug of choice for the first-line treatment of type 2 diabetes. According to broadly accepted guidelines, it should be administered early at diagnosis of this metabolic disorder, alongside diet and exercise. This agent may also be safely and efficaciously combined with all other oral hypoglycemic agents, enabling a useful additive effect. Additionally, it may be prescribed in conjunction with insulin. This combination aims to offset insulin resistance, reduce insulin requirements and minimize weight gain. Of greater importance, metformin has been consistently shown to have a favorable effect on cardiovascular risk factors and to improve cardiovascular outcomes. Interestingly, the efficacy of metformin is accompanied by excellent safety: caution is only needed to avoid the drug in patients with obvious contraindications (mainly chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, liver disease). Moreover, the cost-effectiveness of metformin has been established. Generally, metformin is an excellent choice both in the specialized setting and in primary health care.
Pharmacotherapy of Paget's Disease of Bone: Focus on Zoledronic Acid
Authors: Tziomalos Konstantinos , Athyros Vasilios G. , Karagiannis Asterios
Published: November 2017

Paget's disease of bone (PDB) affects 1%-3% of the population and is associated with increased risk for bone fracture and deformity. Increased osteoclastic activity is the principal characteristic of PDB. Bisphosphonates inhibit osteoclastic activity and represent the mainstay of treatment of PDB. Zoledronic acid, a potent member of this class, normalizes serum alkaline phosphatase (ALP) levels in the majority of patients with PDB and induces sustained disease remissions. It appears to be more effective than both risedronate and pamidronate. However, it is not clear whether bisphosphonates, including zoledronic acid, improve the clinical outcome of patients with PDB. Zoledronic acid was associated with increased risk for atrial fibrillation and osteonecrosis of the jaw in some studies in patients with osteoporosis and cancer, respectively, but not in patients with PDB. Until we have data on the effects of bisphosphonates on clinical outcomes in PDB such as fracture, deformity and osteosarcoma, we must base therapeutic decisions on the data regarding the effects of these agents on disease activity markers (such as serum ALP levels) and bone pain.
Bevacizumab: Its Place in the Treatment of Advanced Non-small Cell Lung Cancer
Authors: Agarwal V , Prasad R , Butt M
Published: November 2017

Lung cancer is the most common cause of cancer mortality worldwide and even with current advances in chemotherapy the outcome is disappointing. The advances in molecular biology have enabled us to identify various targets for anticancer treatments. The VEGF-VEGFR signalling pathway plays a significant role in tumor angiogenesis and has been a major target for the development of various anticancer drugs. Bevacizumab is a recombinant humanized monoclonal antibody, which binds to VEGF and has shown efficacy in various tumors. Bevacizumab has been licensed in first line treatment of non-small cell lung cancer (NSCLC) in combination with chemotherapy. We are reviewing the evidence of the benefit and toxicity of Bevacizumab in combination with chemotherapy and other targeted agents in advanced NSCLC.
A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions
Authors: Ryu Jubin , Yang F. Clarissa
Published: November 2017

Imiquimod (trade name Aldara™) is a small molecule of the imidazoquinoline family, a group of nucleoside analogs that were first synthesized as potential antiviral agents. It has since been discovered to activate both innate and adaptive immunity, as well as apoptosis. Clinically, it has been approved for three indications thus far: external genital warts, actinic keratosis, and superficial basal cell carcinoma. In addition to these applications, a number of off-label uses have been reported in the literature. In this review, we summarize and discuss the literature describing imiquimod's mechanism of action, its approved and off-label clinical uses, and its safety and tolerability.
Fixed-dose Combination Therapy in Hypertension: Focus on Fixed-dose combination of Amlodipine and Valsartan (Exforge®)
Authors: Aslam Shakil
Published: November 2017

Hypertension is the leading cause of disability and cardiovascular mortality world-wide. Approximately one-third of the US adult population and over a billion people world-wide have hypertension. Despite increased awareness of hypertension and availability of many effective antihypertensive agents, only one third of patients achieve their target blood pressure (BP). All expert panels now recommend use of combination therapy for stage 2 and higher hypertension and for individuals who are at increased risk of cardiovascular disease (CVD). Amlodipine, a dihydropyridine calcium channel blocker and Valsartan, an angiotensin II receptor (AT1-R) antagonist are widely used antihypertensive agents. Their efficacy in lowering systolic and diastolic BP and reducing CVD events has been demonstrated in several randomized trials. Fixed-dose combination of amlodipine and valsartan (A/V) has been shown to be more effective in lowering BP than monotherapy with either of these agents alone in randomized trials with comparable side effect profile. Approximately 80%-90% of patients with stage 1-2 hypertension receiving A/V fixed-dose combination achieve significant response, defined as a mean sitting diastolic BP < 90 mmHg or > 10 mmHg reduction from the baseline. Subgroup analyses show that A/V fixed-dose combination is equally effective in older individuals (>65), Blacks, in patients with isolated systolic hypertension, and in those who fail monotherapy. Furthermore, A/V fixed-dose combination is well tolerated and simplifies antihypertensive regimen enhancing patient adherence and a better BP control compared to monotherapy.
Aliskiren for the Treatment of Hypertension: An Update
Authors: Lam S , Saxena S , Macina LO , Lester PE
Published: November 2017

Hypertension can lead to significant morbidity and mortality, and requires lifestyle modifications with or without drug therapy to achieve target blood pressure control. Various classes of anti-hypertensive medications are available to healthcare providers. Choice of medications is based not only on efficacy but also tolerability and cost. Aliskiren is the first drug of a new class of agents known as renin inhibitors. It is approved by the U.S. Food and Drug Administration (FDA) as monotherapy or combination therapy with other antihypertensive agents to optimize blood pressure control. Its efficacy in blood pressure reduction is superior to placebo and comparable to angiotensin receptor blockers, hydrochlorothiazide, angiotensin-converting-enzyme inhibitors and atenolol. It also offers additional blood pressure reduction when used in combination of other agents. Recently, a study demonstrated its efficacy and safety in the elderly, and a study suggested its renoprotective effects in patient who were already taking losartan. More clinical studies are awaited to assess its potential for cardiovascular disease risk reduction. This paper reviews the pharmacology, efficacy and safety of aliskiren for the treatment of hypertension.
Pharmacotherapy Options in Rheumatoid Arthritis: Focus on Tocilizumab, a Recombinant Humanized Anti-Interleukin-6 Receptor Antibody
Authors: Ohsugi Yoshiyuki , Kishimoto Tadamitsu
Published: November 2017

Evidence has accumulated indicating that proinflammatory cytokines play critical roles in the pathogenesis of RA. Recent clinical studies demonstrate that blockade of IL-6 signaling with tocilizumab, a recombinant humanized anti-interleukin-6 receptor antibody, is a new therapeutic option for the treatment of patients with RA refractory to conventional DMARD therapy and anti-TNF-α therapy. This paper discusses possible mechanisms of action, reviews the results of clinical trials, and discusses the place of tocilizumab in RA treatment.
Ropinirole in the Treatment of Restless Legs Syndrome
Authors: Vetrugno Roberto , Montagna Pasquale
Published: November 2017

Restless Legs Syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and an irresistible urge to move them to relieve discomfort. Evidence-based guidelines consider dopaminergic therapy to be the mainstay of treatment for RLS. Ropinirole is a modern, non-ergoline dopamine agonist which has been widely studied for the treatment of moderate-to-severe primary RLS. Data from placebo-controlled studies show that ropinirole significantly improves the symptoms of RLS. These improvements are supported by data from individual studies and pooled analyses. In addition, ropinirole significantly enhances the objective measures of RLS motor symptoms, such as periodic leg movements, and subjective measures of sleep. Ropinirole is generally well-tolerated, but a newly developed extended-release formulation may benefit patients who warrant an extended duration of therapy.
Pharmacokinetics of Lopinavir in the LPV/R-Meltrex Formulation Compared to the LPV/R-Soft Gelatine Capsule in HIV Infected Patients
Authors: Leyh Matthias , Zipperich Sven , Winzer Ralf , Drechsel Philipp , Bogner Johannes , Trein Andreas , Schneider Lothar , Klinker Hartwig , Langmann Peter
Published: November 2017

The protease inhibitor Lopinavir (LPV) combined with low dose ritonavir (r) in the formulation of a soft gelatine capsule (SGC) has been widely used in antiretroviral therapy and has been shown to produce safe therapeutic plasma levels. In June 2006, the LPV/r combination was approved as a tablet (TBL) in Germany and since then has replaced the capsule form. The purpose of this study was to analyze and compare pharmacokinetics of Lopinavir both in the new meltrex tablet formulation and the LPV/r soft gelatine capsule during long-term treatment of HIV.

Methods

Included in this study were all patients followed at multiple study centers between January 2003 and August 2007 for whom LPV plasma levels were archived during therapeutic drug monitoring. A total of 4010 LPV plasma levels from 721 patients met these inclusion criteria. From these, those patients for whom complete data sets were missing were excluded from the study. Complete data sets were defined as those data that included information regarding cumulative daily dose, the patient's anti-retroviral drug regimen, and the time of measurement after drug intake. A total of 571 LPV plasma levels from 138 patients met the full criteria for inclusion in this retrospective study. Additionally, a small prospective study of LPV plasma levels in 6 patients with 24 data points was conducted in order to increase the reliability of this report.

Results

At 3 h after dosing, plasma levels of LPV were significantly higher in patients who had received the meltrex tablet (Mdn = 10030 ng/ml, min = 3323, max = 17280) compared to those who had received the soft gelatine capsule (Mdn = 7964 ng/ml, min = 120, max = 17900). This difference was statistically significant (p < 0.05). There were no statistically significant differences between the LPV plasma levels of the tablet and the capsule at 6, 9 and 12 h after dosing. Additionally, there were no differences between the trough levels of LPV in the two formulations. However, great variances of plasma levels were detected at time 12 h after dosing for both treatment groups (s(capsule) = 3213 ng/ml, s(tablet) = 2273 ng/ml).

Conclusion

The LPV/r tablet formulation is able to produce equivalent to significantly higher plasma levels of LPV when compared with the SGC formulation at time 3 h after drug intake. In addition, the known sex difference in the pharmacokinetic profile of the tablet formulation was verified in this study.
Present and Prospective Pharmacotherapies in Pulmonary Arterial Hypertension
Authors: Johnson Jennifer A. , Hemnes Anna R.
Published: November 2017

Pulmonary arterial hypertension (PAH) is a progressive disease leading to obstruction of the small pulmonary arteries. Currently, there are eight approved medications for PAH. This review article focuses on the mechanisms, clinical trials, efficacy, and safety profiles of each of the PAH medications. In addition, this review addresses combination PAH therapy, patient preference, and future therapies.
Tetrabenazine in Huntington's Disease Chorea
Authors: Chitnis Shilpa , Karunapuzha Cherian Abraham
Published: November 2017

Huntington's disease (HD) is a heredodegenerative neurological disorder with chorea and other hyperkinetic movement disorders being part of the disease spectrum. These along with cognitive and neurobehavioral manifestations contribute significantly to patient's disability. Several classes of drugs have been used to treat the various symptoms of HD. These include typical and atypical neuroleptics along with dopamine depletors for treatment of chorea and antidepressants, GABA agonists, antiepileptic medications, cholinesterase inhibitors, antiglutamatergic drugs and botulinum toxin for treatment of other manifestations. Tetrabenazine (TBZ), a dopamine depleting medication was recently approved by the US FDA for treatment of chorea in HD. The purpose of this article is to briefly review information regarding HD and current treatments for chorea and specifically focus on TBZ and review the literature related to its use in HD chorea.
Antipsychotic Drug Treatment for Patients with Schizophrenia: Theoretical Background, Clinical Considerations and Patient Preferences
Authors: Nielsen René Ernst , Nielsen Jimmi
Published: November 2017

The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed increased efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.
Palonosetron Hydrochloride in the Treatment of Chemotherapy-Induced Nausea and Vomiting
Authors: Li Quan , Roddy Julianna V.F. , Berger Michael
Published: November 2017

Chemotherapy-induced nausea and vomiting (CINV) is among the most unpleasant and stressful aspects of chemotherapy. Poorly controlled nausea and vomiting may have negative impacts on clinical treatment and quality of life. Clinical trials aimed at the prevention of CINV have focused on both acute and delayed phases of CINV. The use of first generation serotonin subtype 3 serotonin (5-HT3) receptor antagonists has significantly improved symptom control in acute CINV. However, they are less effective in controlling delayed CINV Palonosetron is a second generation 5-HT3 receptor antagonist with high potency, selectivity, prolonged half-life, and a unique allosteric binding mechanism. Previous trials which compared palonosetron to other first generation 5-HT3 antagonists had used the prevention of delayed CINV as a secondary end point. Recent data have demonstrated palonosetron, when used with a corticosteroid, was superior to granisetron in the prevention of delayed CINV as a primary end point. This article will review recently published literature focusing on mechanism of action, metabolism, pharmacokinetics, clinical efficacy, and safety of palonosetron in the treatment of CINV, specifically delayed CINV.
Safety and Efficacy of Eplerenone in the Management of Essential Hypertension
Authors: McManus Frances , Connell John
Published: November 2017

Suppression of the Renin-Angiotensin-Aldosterone system (RAAS) is an established intervention in the management of cardiovascular disease. Large, randomized controlled trials have provided a sound evidence base for the use of mineralocorticoid receptor antagonists to block the end product of the RAAS in the treatment of heart failure. However, the place for mineralocorticoid blockade in the treatment of hypertension is less well defined and lacking a strong evidence base. The main indication for the use of this strategy in hypertension is as a third line agent in the treatment of refractory hypertension. The most widely used mineralocorticoid receptor antagonist, spironolactone, is associated with dose related sexual side effects, limiting its use in clinical practice. Eplerenone, the selective mineralocorticoid receptor antagonist, is a promising cardiovascular drug licensed for the treatment of heart failure in Europe and heart failure and hypertension in the USA. It effectively blocks the mineralocorticoid receptor without the unpleasant sexual side effect profile of spironolactone. We review the use of eplerenone, a selective mineralocorticoid receptor antagonist in the treatment of hypertension; discuss its mechanism of action, safety profile as well as its current place in therapy.
Pharmacotherapy of Candida Infections with Echinocandins
Authors: Espinel-Ingroff Ana , Canton Emilia , Martin-Mazuelos Estrella , Pemán Javier
Published: November 2017

The classic recommended antifungal agents for the treatment of invasive Candida infections were amphotericin B, a lipid formulation of amphotericin B and fluconazole in both neutropenic or nonneutropenic patients as either primary or alternative therapies. Voriconazole has been recommended when additional coverage for filamentous fungi is needed (e.g. neutropenic patients). More recently and based on well designed comparative clinical trials, the three echinocandins, caspofungin, anidulafungin and micafungin have been added as primary or alternative therapies especially for critically ill or neutropenic patients. In general, the echinocandins are most useful when patients have previously been exposed to an azole or are unstable.
Temsirolimus: A Review of its Use in the Treatment of Advanced Renal Cell Carcinoma
Authors: Chan Fanny , Samlowski Erika E. , Samlowski Wolfram E.
Published: November 2017

The mTOR (mammalian target of rapamycin) signaling pathway was discovered during studies of the immunosuppressive agent rapamycin. This pathway regulates cell growth, protein synthesis and angiogenesis in response to environmental factors. The mTOR complex-1 inhibitor temsirolimus was derived from rapamycin to have less immunosuppressive and improved solubility characteristics. The safety, tolerability and efficacy of temsirolimus have been well established in clinical trials. Drug related toxicity included rash, mucositis, asthenia, nausea, hyperglycemia, hypophosphatemia, anemia, and hypertriglyceridemia. An active and well-tolerated single agent dose is 25 mg i.v. weekly. A large Phase III trial in poor-prognosis patients with metastatic renal cancer compared i.v weekly temsirolimus administration to subcutaneous interferon alpha (IFNα), or a combination of temsirolimus plus IFNα. This study established that median overall survival was improved to 10.9 months in the temsirolimus group compared to 7.3 months in IFNα-treated group (0.73 hazard ratio for death; 95% confidence interval [CI], 0.58 to 0.92; P = 0.008). A modest objective response rate of 8.6%, 4.8%, and 8.1%, respectively was observed in the three groups, associated with a median time to treatment failure of 3.8 months for temsirolimus alone, 1.9 months for IFNα, and 2.5 months for the combination. These results led to approval of temsirolimus for the treatment of renal cancer in the United States. Temsirolimus is clearly indicated for first-line therapy of Motzer “poor risk” renal cancer and aggressive non-clear cell renal cancer. Temsirolimus may be useful after failure of VEGF tyrosine kinase inhibitors. Clinical activity in other tumor types, such as endometrial cancer has been observed. Temsirolimus is therefore an important new agent for cancer treatment.
Pharmacotherapy of Chronic Obstructive Pulmonary Disease: Focus on Arformoterol Tartrate
Authors: King Paul T
Published: November 2017

Arformoterol tartrate is a newly developed long-acting ssβ2-agonist with both acute and prolonged bronchodilator effects. It is formed of 2 isomers (R,R/R,R) which distinguishes it from the more commonly used racemic formoterol (R,R/S,S). The active isomer is the (R,R) and in vitro arformoterol may have more potent anti-inflammatory effects than formoterol. It can only be given by a nebulizer. There have been 5 randomized, blinded trials which have assessed the use of arformoterol in chronic obstructive pulmonary disease (COPD). Arformoterol has been demonstrated to improve lung function and symptoms but the subjects tested did have a high degree of airway reactivity. The medication was well tolerated with a low incidence of side effects but the trials may not have been of sufficient duration to assess this adequately. Arformoterol should be used with caution in subjects with underlying cardiac disease. The current main use of arformoterol is in those subjects with COPD who require a long acting β2-agonist but who cannot use a dry powder or metered dose inhaler preparation. Arformoterol may only need to be given once a day and can be combined with other inhaled medication particularly tiotropium for additional benefit. It potentially has a role in the management of acute exacerbations.
Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension
Authors: Valerio Christopher J , Kabunga Peter , Coghlan John G
Published: November 2017

Three different classes of specific therapy exist for pulmonary arterial hypertension. Ambrisentan belongs to the endothelin receptor antagonist (ERA) class of drugs, which inhibit the action of Endothelin-1; a potent vasoconstrictor and mitogen. Unlike bosentan and sitaxentan, it has a propanoic-acid based structure and like sitaxentan it has selective affinity for type A Endothelin receptors. Two large randomized controlled trials (ARIES-1 and ARIES-2) have demonstrated clinical benefit with ambrisentan in pulmonary arterial hypertension by repeated measurement of 6-minute walk distance. The most common adverse effect associated with ambrisentan use is peripheral edema, the incidence of liver enzyme elevation seen is lower than for other ERAs. Ambrisentan is safe in combination with warfarin and sildenafil. It offers further flexibility in the treatment of PAH as monotherapy and in combination. Although encouraging, trial data do not exhibit improved efficacy compared with other ERAs or sildenafil and there are no direct comparison studies. Long-term outcome data, including subgroup analysis are awaited to see if there are particular benefits of this therapy in PAH.
Safety and Efficacy of Doxycycline
Authors: Leggat Peter A.
Published: November 2017

Doxycycline has remained one of the most commonly used and inexpensive of the broad-spectrum antibiotic drugs currently in use. It has a variety of applications to common respiratory and genitourinary tract infections, but also amongst atypical infections, such as malaria, rickettsial infections, leptospirosis, brucellosis and some of the bioterrorist agents, including anthrax. It is known that the tetracycline class of antibiotics does have a range of side-effects, such as photosensitivity and gastrointestinal side effects, and noteworthy contraindications, especially amongst pregnant women and young children.
Zolmitriptan and the Triptan Era
Authors: Marmura Michael J.
Published: November 2017

Zolmitriptan is one of seven triptans available to treat acute migraine attacks. The introduction of these selective serotonin receptor agonists almost 20 years ago has revolutionized acute migraine treatment. Triptans are now first line migraine drugs, and provide acute treatment that is well-tolerated, safe and effective. This commentary reviews the use of zolmitriptan and other triptans, discusses how to maximize their effect, and examines the controversies surrounding this class of medication such as medication-overuse headache, use in migraine aura or prodrome, pediatric use, and important drug interactions.
Triptans in the Treatment of Migraine
Authors: Guldiken Baburhan
Published: November 2017

Migraine is a neurovascular disease, which pathogenesis is still unclear. It causes a severe headache and a substantial financial loss due to absenteeism, therefore, its effective treatment is particularly valuable. Triptans, selective 5HT1B and D receptor agonists, are effective treatment choices of acute migraine attacks. Migraine patients, who bear special conditions such as hypertension, hepatic or renal impairment, constitute a special subgroup of patients whose treatment with triptans has to be individually arranged. The review of Kalanuria and Peterlin, regarding the metabolism and efficacy of zolmitriptan in the abortive treatment of migraine, highlights many details of the use of zolmitriptan in migraine patients.
Current Rational to Prescribe Tigecycline: Critical Analysis of the Evidence and Usage Algorithms by an Argentinean Experts Panel
Authors: Curcio Daniel , Barcelona Laura I. , Cornistein Wanda , Bantar Carlos , Barcan Laura , Bonvehí Pablo , Reina Rosa , Bergallo Carlos , Biondi Héctor , Calderón Jorge , Castagnino Jorge , Chinchilla Paulo , Dignani María Cecilia , Esposto Amadeo , Pérez Norma Falcón , Freuler Cristina , Luna Carlos M. , Ríos Fernando , Rodriguez Claudia , valentini Ricardo , Vazquez Walter , verbanaz Sergio , vergara Gabriel
Published: November 2017

Tigecycline is the first of a new class of antibiotics named glycylcyclines and is active in vitro against a variety of gram-positive and gram-negative organisms, including nosocomial resistant pathogens such as vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Enterobacteriaceae, and multidrug-resistant- Acinetobacter spp. This medication has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections (cIAI), complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia. Tigecycline's pharmacological and microbiological profile has also encouraged physicians’ to use the drug in other infections caused by resistant pathogens featuring limited therapeutics options (i.e. hospital-acquired pneumonia-HAP). In this study we publish the conclusions of an expert panel that identify and evaluate the evidence to support the use of Tigecycline in hospitalized patients with one of the following three infections: cSSSI, cIAI and HAP, including ventilator-associated pneumonia. Based on this data the panel developed an Algorithm Rational to Prescribe Tigecycline (ART) for each pathology.
Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women
Authors: Milani Monica , Jha Gautam , Potter David A.
Published: November 2017

The majority of breast cancers express the estrogen receptor and depend on estradiol (E2) for their growth. Hormonal therapy aims at depriving estrogen signaling either by using selective estrogen receptor modulators (SERM)–-that interfere with the binding of E2 to its receptor (ER)–-or aromatase inhibitors (AI)–-that block the aromatase-dependent synthesis of E2. While SERMs are recommended for both pre- and post-menopausal patients, AIs are indicated only for post-menopausal patients. For the past 20 years, the SERM tamoxifen has been considered the “gold standard” for the treatment of hormone receptor positive breast cancers. However, tamoxifen's role is now challenged by third generation AIs, such as anastrozole, which exhibit greater efficacy in the adjuvant setting in several recently reported trials. This review will focus on anastrozole's mechanism of action, dosing, pharmacology, pharmacokinetics, and clinical applications. It will briefly discuss the clinical trials that determined anastrozole's efficacy in the treatment of advanced breast cancer (ABC) and in the neo-adjuvant setting. Finally, it will present the clinical trials that established anastrozole as a frontline agent in the treatment of post-menopausal women with hormone receptor positive early breast cancer.
Study of Specific Dermatoses of Pregnancy and Skin Diseases affected by Pregnancy in a Tertiary Care Rural Hospital
Authors: Khare Stuti , Singh Adarshlata
Published: November 2017

Aims and objectives: To study the various specific dermatoses of pregnancy and changes due to pregnancy.

Study design: A cross-sectional study was conducted in a tertiary care center, Department of Dermatology and Department of Obstetrics and Gynecology.

Materials and methods: A total of 400 pregnant females were enrolled and studied for various cutaneous changes of pregnancy. In pregnant females with specific dermatoses of pregnancy, detailed clinical examination was done regarding the morphology, pattern, and distribution of lesions. Routine blood investigations were done in all pregnant females. Biopsy was done wherever required.

Results: Among 400 pregnant females, we found 38 (9.5%) to be having specific dermatosis of pregnancy. The most common specific dermatosis of pregnancy was prurigo of pregnancy (4.75%), followed by pruritic urticarial papules and plaques (PUPP) of pregnancy (4%), intrahepatic cholestasis (ICP) of pregnancy (0.25%), and pruritic folliculitis of pregnancy (0.125%). In 9.5% females, skin diseases were caused due to pregnancy.
Ectopic Tooth in the Anterior Wall of Maxillary Sinus
Authors: Surana Sanidhya , Thakur Deepak , Kapse Sheetal , Kashyap Mukesh
Published: November 2017

A 16-year-old male patient reported to our department with a chief complaint of pain and swelling in the upper left cheek region. On examination, a maxillary canine was found ectopically in the anterior wall of maxillary sinus. Ectopic eruption of teeth into regions other than the oral cavity is rare. We present one such case of ectopic eruption of maxillary canine.
Chemical characterization and source identification of PM2.5 at multiple sites in the Beijing–Tianjin–Hebei region, China
Authors: Huang Xiaojuan , Liu Zirui , Liu Jingyun , Hu Bo , Wen Tianxue , Tang Guiqian , Zhang Junke , Wu Fangkun , Ji Dongsheng , Wang Lili , Wang Yuesi
Published: November 2017

Abstract. The simultaneous observation and analysis of atmospheric fine particles (PM2.5) on a regional scale is an important approach to develop control strategies for haze pollution. In this study, samples of filtered PM2.5 were collected simultaneously at three urban sites (Beijing, Tianjin, and Shijiazhuang) and at a regional background site (Xinglong) in the Beijing–Tianjin–Hebei (BTH) region from June 2014 to April 2015. The PM2.5 at the four sites was mainly comprised of organic matter, secondary inorganic ions, and mineral dust. Positive matrix factorization (PMF) demonstrated that, on an annual basis, secondary inorganic aerosol was the largest PM2.5 source in this region, accounting for 29.2–40.5 % of the PM2.5 mass at the urban sites; the second-largest PM2.5 source was motor vehicle exhaust, particularly in Beijing (24.9 %), whereas coal combustion was also a large source in Tianjin (12.4 %) and Shijiazhuang (15.5 %), with particular dominance in winter. Secondary inorganic aerosol plays a vital role in the haze process, with the exception of the spring haze in Shijiazhuang and Tianjin, for which the dust source was crucial. In addition to secondary transformations, local direct emissions (coal combustion and motor vehicle exhaust) significantly contribute to the winter haze at the urban sites. Moreover, with the aggravation of haze pollution, the OC ∕ EC mass ratio of PM2.5 decreased considerably and the nitrate-rich secondary aerosol increased during all four seasons in Beijing, both of which indicate that local motor vehicle emissions significantly contribute to the severe haze episodes in Beijing. To assess the impacts of regional transport on haze pollution, the PMF results were further processed with backward-trajectory cluster analysis, revealing that haze pollution usually occurred when air masses originating from polluted industrial regions in the south prevailed and is characterized by high PM2.5 loadings with considerable contributions from secondary aerosols. This study suggests that control strategies to mitigate haze pollution in the BTH region should focus on the reduction of gaseous precursor emissions from fossil fuel combustion (motor vehicle emissions in Beijing and coal combustion in Tianjin, Hebei, and nearby provinces).
Quantifying errors in surface ozone predictions associated with clouds over CONUS: A WRF-Chem modeling study using satellite cloud retrievals
Authors: Ryu Young-Hee , Hodzic Alma , Barre Jerome , Descombes Gael , Minnis Patrick
Published: November 2017

Abstract. Clouds play a key role in radiation and hence O3 photochemistry by modulating photolysis rates and light-dependent emissions of biogenic volatile organic compounds (BVOCs). It is not well known, however, how much error in O3 predictions can be directly attributed to that in cloud predictions. This study applies the Weather Research and Forecasting with Chemistry (WRF-Chem) at 12 km horizontal resolution with the Morrison microphysics and Grell 3D cumulus parameterization to quantify uncertainties in summertime surface O3 predictions associated with the cloudiness over contiguous United States (CONUS). To evaluate the model's own clouds and to restrain the growth of model errors, the model is driven by reanalysis atmospheric data and reinitialized every 2 days. In sensitivity simulations, cloud fields used for photochemistry are corrected based on satellite cloud retrievals. The results show that WRF-Chem predicts about 55 % of clouds in the right locations and generally underpredicts cloud optical depths. These errors in cloud predictions can lead up to 60 ppb overestimation in hourly surface O3 concentrations on some days. The average difference in summertime surface O3 concentrations derived from the modeled clouds and satellite clouds ranges from 1 to 6 ppb for the 8-h average O3 over CONUS. This represents up to ~ 40 % of the total 8-h average O3 bias under cloudy conditions in the tested model version, and the results are robust with respect to the choice of the microphysics scheme. Surface O3 concentrations are sensitive to cloud errors mainly through the calculation of photolysis rates (for ~ 80 %), and to a lesser extent to light-dependent BVOC emissions. The sensitivity of surface O3 to satellite-based cloud corrections is about 2 times larger in VOC-limited than NOX-limited regimes. Our results suggest that the benefits of accurate predictions of cloudiness would be significant in VOC-limited regions which are typical of urban areas.
Searching for the 27-day solar rotational cycle in lightning events recorded in old diaries in Kyoto from the 17th to 18th century
Authors: Miyahara Hiroko , Aono Yasuyuki , Kataoka Ryuho
Published: November 2017

Abstract. A solar rotational period of approximately 27 days has been detected in cloud and lightning activities, although the mechanism of the sun–climate connection remains unclear. In previous studies, lightning activity in Japan showed a significant signal of the solar rotational period, especially around the maxima of the decadal solar cycles. Here we analyze the time series of lightning activity in the AD 1668–1767 period, extracted from old diaries in Kyoto, Japan, and search for the signal of solar rotational cycles. The 27-day cycles were detected in the lightning data and occurred only around the maxima of the decadal sunspot cycles. The signal disappeared during AD 1668–1715, which corresponds to the latter half of the Maunder Minimum when both radiative and magnetic disturbances were thought to have been weak. These findings provide insight into the connection between solar activity and the Earth's climate.
Global consequences of afforestation and bioenergy cultivation on ecosystem service indicators
Authors: Krause Andreas , Pugh Thomas A. M. , Bayer Anita D. , Doelman Jonathan C. , Humpenöder Florian , Anthoni Peter , Olin Stefan , Bodirsky Benjamin L. , Popp Alexander , Stehfest Elke , Arneth Almut
Published: November 2017

Abstract. Land management for carbon storage is discussed as being indispensable for climate change mitigation because of its large potential to remove carbon dioxide from the atmosphere, and to avoid further emissions from deforestation. However, the acceptance and feasibility of land-based mitigation projects depends on potential side effects on other important ecosystem functions and their services. Here, we use projections of future land use and land cover for different land-based mitigation options from two land-use models (IMAGE and MAgPIE) and evaluate their effects with a global dynamic vegetation model (LPJ-GUESS). In the land-use models, carbon removal was achieved either via growth of bioenergy crops combined with carbon capture and storage, via avoided deforestation and afforestation, or via a combination of both. We compare these scenarios to a reference scenario without land-based mitigation and analyse the LPJ-GUESS simulations with the aim of assessing synergies and trade-offs across a range of ecosystem service indicators: carbon storage, surface albedo, evapotranspiration, water runoff, crop production, nitrogen loss, and emissions of biogenic volatile organic compounds. In our mitigation simulations cumulative carbon storage by year 2099 ranged between 55 and 89 GtC. Other ecosystem service indicators were influenced heterogeneously both positively and negatively, with large variability across regions and land-use scenarios. Avoided deforestation and afforestation led to an increase in evapotranspiration and enhanced emissions of biogenic volatile organic compounds, and to a decrease in albedo, runoff, and nitrogen loss. Crop production could also decrease in the afforestation scenarios as a result of reduced crop area, especially for MAgPIE land-use patterns, if assumed increases in crop yields cannot be realized. Bioenergy-based climate change mitigation was projected to affect less area globally than in the forest expansion scenarios, and resulted in less pronounced changes in most ecosystem service indicators than forest-based mitigation, but included a possible decrease in nitrogen loss, crop production, and biogenic volatile organic compounds emissions.