Cubosomes: an overview

Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of water with a microstructure that provides unique properties of practical interest. The discovery of cubosomes is a unique story and spans the field of food science, differential geometry, biological membranes and digestive processes. One of the most common surfactants used to make cubosomes is the monoglyceride glycerol monoolein. Bicontinuous cubic liquid crystalline phase is an optically clear, very viscous material that has a unique structure at the nanometer scale. The word bicontinuous refers to the division of the two continuous but non-intersecting aqueous regions by a lipid bilayer that is contorted into a space-filling structure. Hydrating a surfactant or polar lipid that forms cubic phase and then dispersing the solid-like phase into smaller particles usually form Cubosomes. There is a lot of excitement about the cubic phases because its unique microstructure is biologically compatible and capable of controlled release of solubilized active ingredients like drugs and proteins.     

Quinupristin-dalfopristin: an overview

Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin. Individually, each component has bacteriostatic activity against staphylococci and streptococci, but together, the agents exhibit synergy, leading to bactericidal activity. The combination drug, however, is bacteriostatic against Enterococcus faecium and has poor activity against Enterococcus faecalis. Despite a short half-life, an extended postantibiotic effect allows the agent to be dosed every 8-12 hours. Both drugs are largely hepatically metabolized and excreted in bile. Although not metabolized by cytochrome P450 3A4, quinupristin-dalfopristin can inhibit agents that are metabolized through this pathway. Dosage adjustments may be necessary in patients with hepatic dysfunction. Alterations in renal function have minimal effects on the agent's pharmacokinetics. Adverse events include arthralgia, myalgias, and infusion-related pain. Based on available data, quinupristin-dalfopristin appears to have a role in treating severely ill patients with infections due to multiresistant gram-positive pathogens.     

Polyanhydrides: an overview

Polyanhydrides have been considered to be useful biomaterials as carriers of drugs to various organs of the human body such as brain, bone, blood vessels, and eyes. They can be prepared easily from available, low cost resources and can be manipulated to meet desirable characteristics. Polyanhydrides are biocompatible and degrade in vivo into non-toxic diacid counterparts that are eliminated from the body as metabolites. Owing to their usefulness, this review focuses on the development, synthesis methods, structures and characterization of polyanhydrides, which will provide an overview for the researchers in the field. Their in vitro and in vivo degradability, toxicity, biocompatibility and applications are discussed in the subsequent chapters of this special issue on polyanhydrides and poly(ortho esters).     

Neurotuberculosis: an overview

Although pulmonary tuberculosis is the most common form of this disease, neurotuberculosis is more severe and presents higher morbidity and mortality. Its diagnosis continues to challenge physicians all over the world. Contributing to this fact is the nonspecificity of its clinical manifestations, the low density of bacilli in the cerebrospinal fluid (CSF), and the delayed recovery of Mycobacterium tuberculosis through culture techniques. Thus, the diagnosis is largely based on suspicious symptoms, and the prognosis is directly related to the stage of the disease at the beginning of treatment. Even thought there is no consensus regarding the best therapeutic regimen, the WHO recommends using the same regimen used for pulmonary tuberculosis with a longer treatment time. It is important to note that in most cases, the doctor will not have a definite diagnosis at the beginning of the treatment. However, this should not delay the initiation of therapy. A delay in initiating treatment, in most cases, is directly associated with a poor prognosis. This review gives an overview of the current state of the neurotuberculosis research. It covers the epidemiological aspects of the infection, pathogenesis, principal clinical presentations, diagnosis highlighting neuroimaging, where a series of imaging are presented, prognosis, prevention and therapeutic regimens.     

Gamma-pyrone compounds. II: Synthesis and antiplatelet effects of tetraoxygenated xanthones.

Norathyriol and its analogues, 1,3,5,6-, 3,4,5,6-, 3,4,6,7- and 2,3,6,7-tetrahydroxyxanthone, were synthesized from benzophenone precursors by Friedel-Crafts acylation and subsequent base-catalyzed cyclization to eliminate methanol. Both 3,4,6,7- and 2,3,6,7-tetrahydroxyxanthone tetraacetate showed potent anti-platelet aggregation effects on arachidonic acid-induced platelet aggregation. 3,4,6,7-Tetrahydroxyxanthone tetraacetate and 1,3,5,6-tetrahydroxyxanthone showed potent and significant anti-platelet aggregation effects on collagen-induced platelet aggregation.     

Diamond-Blackfan Anaemia: an overview

Diamond Blackfan Anaemia (DBA) is a congenital disease characterised by defective erythroid progenitor maturation. It is usually diagnosed during the first year of life. The main clinical sign is profound isolated normochromic or macrocytic anaemia, with normal numbers and function of the other haemopoietic cells. Reticulocyte counts in patients with DBA are very low. Bone marrow reflects the defective erythropoiesis, showing a very low number of erythropoietic precursors and a reduction of erythroid burst-forming unit progenitor cells. The proliferation and differentiation of the other lineages are normal. More than one-third of patients have malformations, most often involving the upper limbs and head, and the urogenital or cardiovascular systems. However, the link between these malformations and defective erythropoiesis is unclear and a defect in a molecule acting on both early embryonic development and haematopoiesis has been proposed. Whereas most cases are sporadic, inheritance is observed in 10% of patients, with a dominant or, more rarely, recessive pattern. One locus on chromosome 19q13.2 encoding ribosomal protein S19 accounts for a quarter of patients with either the dominant or the sporadic form. Families not linked with this locus have also been described. The diagnosis of DBA may be difficult and differential diagnoses include Fanconi's anaemia and acquired erythroid aplasias. Erythrocyte adenosine deaminase levels are generally high in DBA patients, which may help in the diagnosis, but they are not pathognomic. Corticosteroids are the main treatment option in DBA and these agents induce erythropoiesis in over 60% of patients. Some patients achieve complete remission, which may be either corticosteroid-induced or spontaneous. The increased in vitro erythropoiesis occasionally induced by the addition of specific cytokines, namely interleukin (IL)-3 and stem cell factor (SCF), has suggested their use in vivo. However, few patients have responded to IL-3, whereas SCF administration, though interesting in theory, has not yet been attempted. Patients who do not respond to corticosteroids and those who have to discontinue treatment because of adverse events must rely on long term transfusions, and are thus exposed to all of the associated complications. Bone marrow or cord blood transplantation has been performed in some patients. The former approach is burdened with severe complications and high mortality.     

Multiple emulsions: an overview

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.     

Poly-L-lactic acid: an overview

In August 2004, the US Food and Drug Administration approved a poly-L-lactic acid (PLLA)-based injectable medical device for restoration and/or correction of the signs of facial fat loss (lipoatrophy) in people with human immunodeficiency virus. As a result, the properties of the PLLA microparticles have received considerable interest from the medical community. Polylactides have a long-standing history of safe use in medical applications, such as pins, plates, screws, intra-bone and soft-tissue implants, and as vectors for sustained release of bioactive compounds. The L-isomer of polylactic acid is a biodegradable, biocompatible, biologically inert, synthetic polymer. Putatively, PLLA microparticles initiate neocollagenesis as a result of a normal foreign-body reaction to their presence. The build-up of collagen over time creates volume at the site of injection, while the PLLA microparticles are metabolized to carbon dioxide and water and expelled through the respiratory system.     

Parenteral microemulsions: an overview

Parenteral delivery of the hydrophobic drugs is a very challenging task. The conventional approaches such as use of co-solvents, oily vehicles and modern approaches such as mixed micelles, liposomes, complexation with cyclodextrins and emulsions have several limitations. Microemulsions have evolved as a novel vehicle for parenteral delivery of the hydrophobic drugs. Their interesting features such as spontaneity of formation, ease of manufacture, high solubilization capacity and self-preserving property make them the vehicle of choice. The review focuses on the excipients available for formulation of the parenteral microemulsions and describes the investigations reported for the various classes of therapeutic agents.     

Group purchasing: an overview

The various types and operational methods of purchasing groups are described, and evaluation of groups is discussed. Since group purchasing is increasing in popularity as a method of controlling drug costs, community and hospital pharmacy managers may need to evaluate various groups to determine the appropriateness of their services. Groups are categorized as independent, system based, or alliance or association based. Instead of "purchasing," some groups develop contracts for hospitals, which then purchase directly from the vendor. Aside from this basic difference between groups that purchase and groups that contract, comparisons among groups are difficult because of the wide variation in sizes and services. Competition developing from diversification among groups has led to "super groups," formed from local and regional groups. In evaluating groups, advantages and disadvantages germane to accomplishing the member's objectives must be considered. To ensure a group's success, members must be committed and support the group's philosophies; hospital pharmacists must help to establish a strong formulary system. To select vendors, groups should develop formal qualification and selection criteria and should not base a decision solely on price. The method of solicitation (bidding or negotiating), as well as the role of the prime vendor, should be studied. Legal implications of group purchasing, especially in the areas of administrative fees and drug diversion, must also be considered. The most advantageous group for each organization will include members with common missions and will be able to implement strategies for future success.     

Ventilator-associated pneumonia: an overview

Despite aggressive efforts to reduce nosocomial infections, many intubated patients develop ventilator-associated pneumonia (VAP). VAP has been an area of intense research; however, there is still little consensus in the literature on how to accurately diagnose or treat VAP. VAP complicates the course of 8 – 28% of mechanically ventilated patients and mortality varies greatly from 8 to 76%, depending on the specific population being studied. Once pneumonia is suspected, bacteriologic confirmation should be obtained and empiric therapy must be instituted as soon as possible, as a delay in therapy or inappropriate therapy greatly increases mortality. Initial antibiotic therapy should be based on the most common organisms in each hospital or unit, and the most likely pathogens for that specific patient. Constant surveillance of the responsible pathogens through the use of antibiograms allows clinicians to make educated choices for antibiotics. When final cultures and sensitivities are available, de-escalation to less broad spectrum antibiotics should be performed. If cultures show no bacterial growth, antibiotics should be discontinued so that patients are not exposed to unnecessary antibiotics. Following these practices will help to decrease multi-resistant strains of bacteria and can improve the morbidity and mortality of VAP.     

Oily skin: an overview

Oily skin (seborrhea) is a common cosmetic problem that occurs when oversized sebaceous glands produce excessive amounts of sebum giving the appearance of shiny and greasy skin. This paper overviews the main concepts of sebaceous gland anatomy and physiology, including the biosynthesis, storage and release of sebum, as well as its relationship to skin hydration and water barrier function. We also address how skin oiliness may vary according to diet, age, gender, ethnicity and hot humid climates. The deeper understanding of this skin type provides the opportunity to better guide patients regarding skin care and also assist in the development of sebosuppressive agents.     

Bipolar depression: an overview

Depressive episodes are significant in bipolar illness since patients can spend up to one-third of their lives in depression. Although the treatment of bipolar depression remains an understudied area, new data from randomized, controlled trials and naturalistic studies have expanded the range of treatments available. The main aim in the treatment of bipolar depression is the prevention of the patient switching to mania and cycle acceleration, and antidepressant therapy may be contraindicated because of the risk for switching. Guidelines for the acute treatment of bipolar depression emphasize treatment with a mood stabilizer, of which lithium has been the most thoroughly studied in randomized, controlled trials in acute bipolar depression. Lamotrigine has also demonstrated significant efficacy in recent studies and has been approved by the FDA.     

Behavioral addictions: an overview

The legitimacy of nonsubstance addictions has received increased attention from clinicians, researchers and the general population as more and more individuals report symptoms consistent with impairment of impulse control. The clinical presentation of these disorders is varied, as compulsive activities may include: gambling, eating, sex, shopping, use of the Internet or videogames or even exercising, working or falling in love. As such, there is great controversy in diagnosing, treating or even naming these conditions, as many of these behaviors are daily rituals instrumental to our ultimate survival. Historically, the phrase "impulse control disorders" described these conditions but many researchers and clinicians also use the term "behavioral addictions," "process addictions" or "impulsive-compulsive behaviors" to report behavioral pathology. This review summarizes the data of each of these behavioral addictions from epidemiology to neurobiology to treatment options. Research suggests similarities between natural and drug reward processing but clinical evidence supports the utilization of treatment modalities for these behavioral conditions that can sometimes differ from traditional drug treatment.     

Diagnostic microspheres: an overview

Diagnostic methods have become increasingly complex and frequently involve the use of agents that must meet the same approval criteria as drugs. The search for diagnostic contrast agents has spread from X-ray to other imaging modalities, especially to magnetic resonance imaging (MRI) and ultrasound. A wide variety of methods have been used to develop microencapsulated agents, from liposomal entrapment to use of biodegradable polymers. Various scientific and technological advancements have been made in the research and development of diagnostic microspheres. Diagnostic microspheres can be used to understand the human body functions in both healthy and sick people. For example, they allow the detection of malignancies vs. benign tissue changes. Diagnostic microspheres give useful clinical information for various diseases, are very stable, and have proven efficacy in the quantitative measurement of blood flow to an organ. This review discusses various aspects of diagnostic microspheres, such as the choice of contrast agents and radioactive molecules, and their applications in blood flow measurements and organ imaging.     

Homocysteine-lowering treatment: an overview

Elevated fasting plasma concentrations of homocysteine have a high prevalence in subjects with cardiovascular disease and have also been associated with an increased risk of atherothrombosis in most, but not all, prospective studies. The most frequent causes of hyperhomocysteinaemia are genetic defects, such as cystathionine-beta-synthase (CBS) deficiency, deficiencies of folic acid and/or vitamin B12, renal failure and interference in homocysteine metabolism by drugs or metabolic alterations. In most cases, no underlying cause can be established. Subjects with CBS deficiency are treated with pyridoxine with additional folic acid and betaine if necessary. Folic acid and vitamin B12 deficiencies should be corrected by supplementation. Increases in folate intake by dietary changes or fortification can also lower plasma homocysteine in vitamin-replete subjects with normal plasma homocysteine levels. In renal failure, folic acid treatment (1-5 mg/day) ameliorates the plasma homocysteine level in most cases but hyperhomocysteinaemia persists in the majority of patients. Primary (fasting) hyperhomocysteinaemia can be treated with folic acid (0.5-5 mg/day). An abnormal methionine-loading test identifies additional patients at risk and postmethionine-loading hyperhomocysteinaemia should be treated with a combination of pyridoxine and folic acid. In the absence of dose-effect studies, a combination of pyridoxine (50 mg) and folic acid (5 mg) is advised. Large clinical trials are currently underway to establish the role of homocysteine-lowering therapy in the secondary prevention of atherothrombotic disease. In view of the effective, cheap and safe character of therapy with folic acid and pyridoxine, a policy can be accepted to screen and treat high-risk patients until these trials have been concluded.     

Carrier erythrocytes: an overview

Application of erythrocytes, the most abundant cells of the human body with desirable physiologic and morphologic characteristics, in drug delivery has been exploited extensively. These cellular carriers, having remarkable biocompatibility, biodegradability, and life-span in circulation, can be loaded by a wide spectrum of compounds of therapeutic value using different chemically, as well as physically, based methods. Most of the characteristics of the erythrocytes, including shape, membrane fragility, deformability, and hematologic indices undergo some degree of irreversible changes during the loading procedure. The efflux pattern of the encapsulated compounds from the carrier erythrocytes covers a wide range between a relatively rapid release (complete release within a few hours) and no detectable release until the cell lysis. A series of methods have been tested successfully for improvement of in vitro storability of the carrier erythrocytes without any significant changes in cell biology as well as drug delivery efficacy. Carrier erythrocytes have been exploited for several potential applications, including intravenous slow release of therapeutic agents, enzyme therapy, drug targeting to reticuloendothelial system (RES), improvement of oxygen delivery to tissues, and preparation of fused cells.