Anatomical and functional imaging techniques: basically similar or fundamentally different?

Accurate and early detection of coronary artery disease (CAD) is essential, as the disease remains one of the leading causes of death in the industrialised world. For this purpose, several invasive as well as noninvasive modalities are available. The current gold standard to detect significant narrowing of the coronary arteries is invasive coronary angiography, which allows direct visualisation of the coronary arteries with high spatial and temporal resolution. In addition, if abnormalities are demonstrated, direct intervention is possible. However, it is also an invasive technique that is associated with substantial patient discomfort, costs and a small but distinct risk of potentially life-threatening complications.     

Dubowitz syndrome: a cholesterol metabolism disorder?

Dubowitz syndrome (DS) (MIM#223370) (4) is a very rare genetic and developmental disorder involving multiple congenital anomalies including: 1) growth failure/short stature; 2) unusual but characteristic facial features; small triangular face, high sloping forehead, ptosis, short palpebral fissures, broad and flat nasal bridge; 3) microcephaly; 4) mild mental retardation; and 5) in at least 50% of the cases, eczema. Multiple organ systems are affected and the disorder is unpredictable and extremely variable in its expression. Here we describe a male Turkish patient who has typical and less common findings of DS with additionally persistently low serum lipid levels and an arachnoid cyst. The present patient is the second case of DS with persistently low cholesterol levels.     

Th17-related cytokines in inflammatory bowel diseases: friends or foes?

T helper (Th)17 cells and other interleukin (IL)-17-producing cells are supposed to play critical roles in several human immune-mediated diseases, including Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man. Th17 cells infiltrate massively the inflamed intestine of IBD patients and in vitro and in vivo studies have shown that Th17-type cytokines may trigger and amplify multiple inflammatory pathways. Nonetheless, some Th17-related cytokines, such as interleukin (IL)-17A and IL-22, may target gut epithelial cells and promote the activation of counter-regulatory mechanisms. This observation together with the demonstration that Th17 cells are not stable and can be converted into either regulatory T cells or Th1 cells if stimulated by immune-suppressive (e.g. TGF-β1) or inflammatory (e.g. IL-12, IL-23) cytokines have contributed to advance our understanding of mechanisms that regulate mucosal homeostasis and inflammation in the gut.     

F.G. syndrome: a rare and/or extremely polymorphic syndrome?

We report a case of mental retardation associated with multiple congenital anomalies suggesting an F.G. syndrome. We discuss problems concerning genetic counselling and the management of future pregnancies. Unfortunately, no concrete strategy, concerning prenatal diagnosis, can be proposed.     

Cytokines and irritable bowel syndrome: Where do we stand?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, which presents with one or more gastrointestinal symptoms without any structural or organic abnormality. The etiology and pathophysiological mechanisms of IBS remain uncertain. Residual or reactivated inflammation at the molecular level is considered the underlying mechanism of post-infectious IBS. On the other hand, genetic variations in the immunological components of the body, including cytokine gene polymorphisms, are proposed as a potential mechanism of IBS even in patients without previous gastrointestinal infection. Several studies have suggested imbalanced cytokine signaling as an etiology for IBS. In this review, recent findings on cytokine profiles and cytokine gene polymorphisms in patients with IBS are described and the role of cytokines in animal models of IBS is discussed.     

Cancer: a single disease with a multitude of manifestions?

The relationships of critical nutrients such as plant phenolics, vitamins, minerals and lipids are considered with respect to the incidence of a variety of cancers, and analyzed in terms of how these nutrient deficiencies alter immune function, DNA integrity and cell proliferation. With a significant correlation found between cancer and these nutrient deficiencies, the hypothesis is presented here that nutrition could provide a unifying perception of cancer and recast it as a single disease. This further suggests that a coordinated administration of specific, critical nutrients to cancer patients could lead to the reversal of the disease. It is also proposed that the concurrent presence of a variety of nutritional deficiencies in cancer patients requires a multilevel, systemic approach to this disease as opposed to the single active therapeutic agent approach that is the cornerstone of contemporary research and pharmacology.     

Do single mitochondria contain zones with different membrane potential?

Observations of Lan Bo Chen’s group using a mitochondria-selective fluorochrome 5,5’,6,6’- tetrachloro- 1,1’,3,3’- tetraethylbenzimidazolocarbocyanine iodide (JC-1) indicate that mitochondria in situ may have zones of different electrochemical potential along their length. This was indicated by the formation of J-aggregates of this dye at distinct sites along a single mitochondrion. Also, intensity variations along single mitochondria were found with diamino-styryl-pyridinium methiodide (DASPMI), another fluorochrome that selectively stains mitochondria depending on their electrochemical potential. DASPMI exchanges easily with the cytoplasm and changes its quantum yield when bound to mitochondrial membranes. Therefore, fluorescence intensity is primarily controlled by the membrane environment rather than by mass accumulation. Two possible explanations of intramitochondrial fluorescence intensity variations have to be discussed: variations in the amount of mitochondrial inner membrane per unit of projection area (or voxel), and differences in the electrochemical gradient. This problem has been approached by comparing fluoro-micrographs of mitochondria in endothelial cells stained with either JC-1 or DASPMI with electron micrographs of the same mitochondria after fixation with glutardialdehyde and osmium tetroxide and ultrathin sectioning. JC-1 red fluorescence (revealing J-aggregate formation) as well as high-intensity staining with DASPMI correlate roughly with the local thickness of mitochondria; no differences in the crista organization are revealed for those areas or mitochondria exhibiting red JC-1 fluorescence and those with green fluorescence. The distance between red fluorescing areas in a single mitochondrion seem to be caused by competition for dye molecules placed in between centres of JC-1 aggregation. Isolated mitochondria are of uniform small size and spherical shape; therefore, no differences in shape interfere with JC-1 staining. Thus JC-1 may be an appropriate indicator of membrane potential in isolated mitochondria. In living cells mitochondria often are large and elongated, and thus the situation is not straightforward to interpret. However, evidence is provided that there are submitochondrial zones, which differ in membrane potential from one adjacent area to another, because DASPMI staining of intramitochondrial zones reveals differences in fluorescence intensity and preferred photodamage of these areas. In some cases separation of the zones of higher membrane potential by cristae traversing the whole diameter of a mitochondrion has been observed. Local photobleaching of stained mitochondria results in a loss of fluorescence along the total length of a mitochondrion. However, this type of bleaching develops over tens of seconds, not in the very short time range (e.g. ms) expected from the discharge of all the membranes if they were electrically coupled.     

Zn- and Cu-thioneins: a functional classification for metallothioneins?

This report intends to provide the reader with a deeper insight in the chemical, and extensively biological, characteristics of the metallothionein (MT) system. We have devoted nearly 20 years to the study of MTs and this has allowed us to form what we believe is a more complete picture of this peculiar family of metalloproteins. At the beginning of the 1990s, the landscape of this field was quite different from the overall picture we have now. Many researchers have contributed to the readjustment of this part of scientific knowledge. In our case, we implemented a unified method for obtaining MTs, for characterizing their metal-binding features, and for applying a unified research rationale. All this has helped to enlarge the initial picture that was mainly dominated by mammalian MT1/MT2 and yeast Cup1, by introducing approximately 20 new MTs. It has also allowed some characteristics to be clarified and examined in more detail, such as the cooperativity or the coexistence of multiple species in the metal-substitution reactions, the availability of Ag(I) or Cd(II) for use as respective probes for the Cu(I) and Zn(II) binding sites, the participation of chloride or sulfide ligands in the metal coordination spheres, and the feasibility of using in vitro data as representative of in vivo scenarios. Overall, the results yield enough data to consider new criteria for a proposal of classification of MTs based on MT metal-binding features, which complements the previous classifications, and that can shed light on the still controversial physiological functions of this peculiar superfamily of metalloproteins.     

Lutzomyia longipalpis in Brazil: a complex or a single species? A mini-review

Lutzomyia longipalpis is the main vector of Leishmania infantum chagasi, the causative agent of American visceral leishmaniasis (AVL). Although there is strong evidence that Lu. longipalpis is a species complex, not all data concerning populations from Brazil support this hypothesis. The issue is still somewhat controversial for this large part of Lu. longipalpis distribution range even though that it is the Latin American region contributing to most of the cases of AVL. In this mini-review we consider in detail the current data for the Brazilian populations and conclude that Lu. longipalpis is a complex of incipient vector species with a complexity similar to Anopheles gambiae s.s. in Africa.     

Plants and animals: a different taste for microbes?

Plants and animals can recognize potential pathogens by detecting pathogen-associated molecular patterns (PAMPs). Significant advances over the past few years have begun to unveil the molecular basis of PAMP perception by pattern recognition receptors (PRRs). Although these discoveries highlight common recognition strategies among higher eukaryotes, they also show differences with respect to the nature of the receptors involved and the exact molecular patterns recognized. This suggests a convergent evolution of microbe sensing by the innate immune systems of these various organisms.     

Complex origins of chloroplast membranes with photosynthetic machineries: multiple transfers of genes from divergent organisms at different times or a single endosymbiotic event?

The paradigm “cyanobacterial origin of chloroplasts” is currently viewed as an established fact. However, we may have to re-consider the origin of chloroplast membranes, because membranes are not replicated by their own. It is the genes for lipid biosynthetic enzymes that are inherited. In the current understandings, these enzymes became encoded by the nuclear genome as a result of endosymbiotic gene transfer from the endosymbiont. However, we previously showed that many enzymes involved in the synthesis of chloroplast peptidoglycan and glycolipids did not originate from cyanobacteria. Here I present results of comprehensive phylogenetic analysis of chloroplast enzymes involved in fatty acid and lipid biosynthesis, as well as additional chloroplast components related to photosynthesis and gene expression. Four types of phylogenetic relationship between chloroplast enzymes (encoded by the chloroplast and nuclear genomes) and cyanobacterial counterparts were found: type 1, chloroplast enzymes diverged from inside of cyanobacterial clade; type 2, chloroplast and cyanobacterial enzymes are sister groups; type 3, chloroplast enzymes originated from homologs of bacteria other than cyanobacteria; type 4, chloroplast enzymes diverged from eukaryotic homologs. Estimation of evolutionary distances suggested that the acquisition times of chloroplast enzymes were diverse, indicating that multiple gene transfers accounted for the chloroplast enzymes analyzed. Based on the results, I try to relax the tight logic of the endosymbiotic origin of chloroplasts involving a single endosymbiotic event by proposing alternative hypotheses. The hypothesis of host-directed chloroplast formation proposes that glycolipid synthesis ability had been acquired by the eukaryotic host before the acquisition of chloroplast ribosomes. Chloroplast membrane system could have been provided by the host, whereas cyanobacteria contributed to the genes for the genetic and photosynthesis systems, at various times, either before or after the formation of chloroplast membranes. The origin(s) of chloroplasts seems to be more complicated than the single event of primary endosymbiosis.

     

Sizeable acquired subglottic cyst in a baby with Williams–Beuren syndrome: Association or coincidence?

We describe a case of an acquired subglottic cyst presented with persistent stridor and voice hoarsening in a baby diagnosed with Williams–Beuren syndrome that was born premature and required intubation during neonatal period. We also comment on whether this is a coincidence or there can be an association between impaired elastogenesis, a feature of patients with the syndrome and the formation of a subglottic cyst.     

Haematemesis: a new syndrome?

Three patients presented with symptoms suggesting a Mallory-Weiss tear. Endoscopy showed a localized, clearly demarcated area of bright red mucosa near the gastro-oesophageal junction; this was thought to have arisen by retrograde intussusception of the stomach during vomiting or retching and may have caused the haemorrhage.     

Mitochondrial stress: a bridge between mitochondrial dysfunction and metabolic diseases?

Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPR^mt) and initiation of a retrograde stress signaling pathway. Defects in the UPR^mt and the retrograde signaling pathways may disrupt the integrity and homeostasis of the mitochondria, resulting in endoplasmic reticulum stress and insulin resistance. Improving the capacity of mitochondria to reduce stress may be an effective approach to improve mitochondria function and to suppress obesity-induced metabolic disorders such as insulin resistance and type 2 diabetes.