Vessel density assessed by endoglin expression in breast carcinomas with different expression profiles

Aims:  To evaluate the relationship between microvessel density assessed by endoglin expression and the molecular subtypes of human invasive breast carcinomas and whether there is evidence to indicate that angiogenesis could be a putative target for therapy in specific subsets of breast cancer.
Methods and results:  We studied a series of 161 breast carcinomas, but information was available on only 142 tumours. We correlated endoglin expression with distinct breast carcinoma subgroups classified according to immunohistochemical profiling. Additionally, we compared it with other biomarkers for the aggressive basal-like subset and with available histopathological data. Although the basal-like subtype has higher microvessel density, there are no significant differences with the other molecular subtypes of breast cancer.
Conclusions:  This study found no significant differences in tumour vascularity in different molecular subtypes of breast cancer.     

Important Factors in the Size Reduction of Polymer-Stabilized Drug Particle Suspensions Using High-Pressure Homogenization

In recent years, high-pressure homogenization has been used with increasing frequency to reduce the size of pharmaceutical suspensions to the micron, submicron, and nano scales with the goal of increasing the dissolution rate of the drug, and consequently, the in vivo bioavailability. As particle suspensions become smaller in size, increased concentrations of surfactants and stabilizers are required to prevent particle agglomeration. Recently, relatively high concentrations of biocompatible polymers have been used to stabilize suspensions by imparting surface-active steric stability as well as kinetic stability through an increase in suspension viscosity and/or a transition to non-Newtonian rheological properties. While the benefits of stable suspensions are known, little is known about the effect of the high polymer concentration on the actual breakup of the particles in suspension. In this work, designed experiments were used to identify the key parameters that govern the final particle size of a drug suspension following homogenization. In particular, drug loading, operating pressure, and polymer concentration were all found to be statistically significant factors in determining the resulting size of particles in suspension. In addition, it was found that an optimal polymer concentration of 2% (w/w) was required to adequately stabilize the particle suspension while simultaneously avoiding a decrease in homogenizer performance. Concentrations higher than 2% (w/w) resulted in size reduction limitations due to the increased viscosity (>10 cP) and the transition to non-Newtonian behavior.     

Contraindications and side effects of commonly used medications in coronary CT angiography

For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the ß-blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies.     

The Almirall European Headache Awards 2009

The Almirall European Headache Awards (AEHA) were organized in conjunction with the European Headache Federation. The awards were held in 2009, aiming to share clinical experience and best practice in headache-related disease management. 56 unusual and challenging cases of headache from 5 European countries (Belgium, France, Italy, Portugal and Spain) were judged by a Scientific Committee including expert representatives from participating countries, acting as reviewers. Three cases were selected from each country. The 15 resulting cases were presented to the Scientific Committee in Madrid, Spain in November 2009 and awards were given to the top 5 presentations. This article presents details of these cases, including the award winning entries. They have been categorized into four main groups: (a) headaches in rare syndromes; (b) secondary headaches to infectious/autoimmune causes or post-trauma/mass occupation; (c) headache in unresolved cases; and (d) other relevant cases. First prize was awarded to a case involving a 55-year-old male with familial thrombocytopenia and a unilateral neuralgiform headache secondary to trigeminal vascular contact, and which was successfully treated with carbamazepine. Conclusions from the meeting include: rare syndromes do occur and require appropriate treatment to improve outcomes; concomitant diseases may impair adequate diagnosis and should be investigated; physicians should be cautious and treat possible serious underlying disease, whilst accurately clarifying the correct diagnosis; neurological examination and complementary tests may be required; consideration should be given to possible rare medication events; and some cases may remain without a clear cause or diagnosis and symptoms should be treated whilst investigations continue.     

Multilocus sequence analysis of Brazilian Rhizobium microsymbionts of common bean (Phaseolus vulgaris L.) reveals unexpected taxonomic diversity

The diazotrophic bacteria collectively known as “rhizobia” are important for establishing symbiotic N₂-fixing associations with many legumes. These microbes have been used for over a century as an environmentally beneficial and cost-effective means of ensuring acceptable yields of agricultural legumes. The most widely used phylogenetic marker for identification and classification of rhizobia has been the 16S rRNA gene; however, this marker fails to discriminate some closely related species. In this study, we established the first multilocus sequence analysis (MLSA) scheme for the identification and classification of rhizobial microsymbionts of common bean (Phaseolus vulgaris L.). We analyzed 12 Brazilian strains representative of a collection of over 850 isolates in addition to type and reference rhizobial strains, by sequencing recA, dnaK, gltA, glnII and rpoA genes. Gene sequence similarities among the five type/reference Rhizobium strains which are symbionts of common bean ranged from 95 to 100% for 16S rRNA, and from 83 to 99% for the other five genes. Rhizobial species described as symbionts of common bean also formed separate groups upon analysis of single and concatenated gene sequences, and clusters formed in each tree were in good mutual agreement. The five additional loci may thus be considered useful markers of the genus Rhizobium; in addition, MLSA also revealed broad genetic diversity among strains classified as Rhizobium tropici, providing evidence of new species.     

Longitudinal growth in chronic hypokalemic disorders

Growth retardation remains a major complication in children with primary tubular disorders, despite adequate supplemental treatment with electrolytes, water and bicarbonate. Chronic hypokalemia, characteristic of some tubulopathies, impairs growth by mechanisms that are not well known. Association with growth hormone deficiency has been reported in patients with Bartter’s or Gitelman’s syndrome. Tissue-specific alterations of growth hormone and insulin-like growth factor I axis have been described in experimental models of potassium depletion. Hypokalemic rats gain less body length and weight than pair-fed normokalemic animals and, by contrast, develop renal hypertrophy. These rats have low circulating concentrations of insulin-like growth factor I, depressed messenger ribonucleic acid (mRNA) levels of this peptide in the tibial growth plate, and they are resistant to the longitudinal growth-promoting effects of exogenous growth hormone. The reason for this resistance remains to be defined. No alterations in the intracellular signaling for growth hormone have been found in the liver of hypokalemic rats. However, treatment with high doses of growth hormone is unable to normalize hypertrophy of the epiphyseal cartilage chondrocytes, which are severely disturbed in potassium depletion and likely play an important role in the pathogenia of growth impairment in this condition.     

Molecular aspects of renal cell carcinoma: a review

Renal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules of the kidney. RCC, the incidence of which is increasing annually, represents five percent of adult epithelial cancers. Clear cell carcinoma represents the most frequent histological subtype. RCC is characterized by a lack of early warning signs, diverse clinical manifestations. Incidentally detected tumors in asymptomatic individuals have been steadily increasing owing to the increased usage of various imaging technologies. Currently there are no recommendations for screening to detect and make an early diagnosis of renal cancer. But in recent years, the discovery of new molecular and cytogenetic markers has led to the recognition and classification of several novel subtypes of RCC, and the introduction of molecular-targeted therapy for advanced-stage RCC. We performed a literature review using PubMed and discuss current knowledge of epidemiology, pathophysiology, evaluation, treatment, and future research directions of RCC.