The role of the fluid phase in the viscous response of bovine periodontal ligament

The mechanical response of the periodontal ligament (PDL) is complex. This tissue responds as a hyperelastic solid when pulled in tension while demonstrating a viscous behavior under compression. This intricacy is reflected in the tissue's morphology, which comprises fibers, glycosaminoglycans, a jagged interface with the surrounding porous bone and an extensive vascular network.In the present study we offer an analysis of the viscous behavior and the interplay between the fibrous matrix and its fluid phase.Cylindrical specimens comprising layers of dentine, PDL and bone were extracted from bovine first molars and affixed to a tensile-compressive loading machine. The viscous properties of the tissue were analyzed (1) by subjecting the specimens to sinusoidal displacements at various frequencies and (2) by cycling the specimens in ‘fully saturated’ and in ‘partially dry’ conditions. Both modes assisted in determining the contribution of the fluid phase to the mechanical response.It was concluded that: (1) PDL showed pseudo-plastic viscous features for cyclic compressive loading, (2) these viscous features essentially resulted from interactions between the porous matrix and unbound fluid content of the tissue. Removing the liquid from the PDL largely eliminates its damping effect in compression.     

FISH in der Diagnostik hämatologischer Neoplasien

All hematological malignancies are characterized by considerable clinical heterogeneity. The diverse entities can be subdivided into a variety of prognosis-defining subtypes on the basis of cytogenetic aberrations and molecular mutations. To adapt the intensity of treatment to the patient’s individual risk profile, an exact classification of the subtypes on the basis of genetic markers is essential. Diverse fluorescent in situ hybridization (FISH) techniques thereby play a central role in interaction with classic chromosome banding analyses for clarifying findings of chromosome analyses, such as in the acute leukemias, or for classifying the diverse subtypes, as in the non-Hodgkin’s lymphomas. Depending on the disease, the clinical impact of FISH varies. It is used as the method of choice for genetic characterization (e.g., in multiple myeloma) or is used in combination with chromosome banding analysis. Furthermore, interphase FISH is essential when rapid confirmation of the diagnosis is needed, as in acute promyelocytic leukemia with the t(15;17)/PML-RARA rearrangement, for which therapy with all-trans retinoic acid (ATRA) should be immediately started.     

Determination of sulfonamide antibiotics by gas chromatography coupled with atomic emission detection

The paper describes the analysis of nine sulfonamides, chosen as the most widely used representatives of an important class of antibacterial drugs. Atomic emission detection has been found to allow simultaneous quantification and identification of the N¹-methylated derivatives, which are resolved efficiently by conventional capillary gas chromatography. Results are given concerning the linearity of the response and the characterization of the individual compounds by the elemental ratio of their carbon, nitrogen and sulfur content. The method looks promising for the quantitative analysis and confirmation of sulfonamide residues in complex mixtures.     

Pränatale Detektion fetaler chromosomaler Aberrationen im 1. und 2. Trimenon

Modern noninvasive methods of prenatal medicine, in particular first-trimester-screening, enable early risk evaluation of the most common forms of aneuploidy. With over 4000 certified gynecologists in Germany, this method nowadays represents the standard in prenatal risk evaluation. The importance of classic genetic sonography during the second trimester by detection of soft markers for aneuploidy has declined. However, detailed sonography during the second trimester remains the gold standard for the detection of congenital anomalies. Therefore, the specialist in prenatal medicine must be able to recognize soft markers during this examination in order to re-evaluate the maternal risk for aneuploidy.     

Ionenkanalerkrankungen des Gehirns – monogene Migräneformen

As opposed to the common, genetically complex types of migraine, there are a few rare monogenic migraine variants. The prototype is familial hemiplegic migraine (FHM), a severe subtype of migraine with aura, for which three causative genes (FHM1–3), all of which are involved in ion translocation in the CNS, have been identified. This review summarizes the current knowledge about the clinical symptomatology, (differential) diagnosis, treatment, genetics, and pathophysiology of FHM. Clinically and genetically overlapping disorders, such as episodic ataxia type 2 (EA-2), spinocerebellar ataxia type 6 (SCA-6) and alternating hemiplegia of childhood (AHC) are briefly discussed, and novel genes which have been occasionally associated with HM or migraine are critically evaluated. Finally, monogenic (vascular) syndromes, in which migraine is part of the phenotypic spectrum, are discussed.     

LNCIB human full-length cDNAs collection: towards a better comprehension of the human transcriptome

LNCIB has been producing a variety of human full-length-enriched, normalized and subtracted cDNA libraries from various cell lines and tissues in different developmental stages by using the CAP-Trapper method. By sequencing 23000 clones of these libraries we identified a pool of about 5800 good quality unique cDNAs. After BLAST analysis on Human RefSeq/Unigene databases, 1717 of these sequences remained with no or poor annotation. We show that cross-species comparative BLAST resulted as a valid tool for the annotation of orthologous genes.     

Sugar and Chromosome Stability: Clastogenic Effects of Sugars in Vitamin B6-Deficient Cells

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, has been implicated in preventing human pathologies, such as diabetes and cancer. However, the mechanisms underlying the beneficial effects of PLP are still unclear. Using Drosophila as a model system, we show that PLP deficiency, caused either by mutations in the pyridoxal kinase-coding gene (dPdxk) or by vitamin B6 antagonists, results in chromosome aberrations (CABs). The CAB frequency in PLP-depleted cells was strongly enhanced by sucrose, glucose or fructose treatments, and dPdxk mutant cells consistently displayed higher glucose contents than their wild type counterparts, an effect that is at least in part a consequence of an acquired insulin resistance. Together, our results indicate that a high intracellular level of glucose has a dramatic clastogenic effect if combined with PLP deficiency. This is likely due to an elevated level of Advanced Glycation End-products (AGE) formation. Treatment of dPdxk mutant cells with α-lipoic acid (ALA) lowered both AGE formation and CAB frequency, suggesting a possible AGE-CAB cause-effect relationship. The clastogenic effect of glucose in PLP-depleted cells is evolutionarily conserved. RNAi-mediated silencing of PDXK in human cells or treatments with PLP inhibitors resulted in chromosome breakage, which was potentiated by glucose and reduced by ALA. These results suggest that patients with concomitant hyperglycemia and vitamin B6 deficiency may suffer chromosome damage. This might impact cancer risk, as CABs are a well-known tumorigenic factor.     

Macroangiopathy in adults and children with diabetes: from molecular mechanisms to vascular damage (part 1).

Type 2 diabetes mellitus (T2DM) is an increasing problem in childhood; however type 1 diabetes mellitus (T1DM) remains by far the most common type of diabetes in this age group. In this review we will focus on T1DM, because this will have the greatest implication for patients diagnosed in childhood. During the atherosclerotic process, several molecular, receptorial and cellular factors provide a continous mechanism of vascular damage. In diabetic children this state seems to be enhanced and facilitated so that accelerated atherosclerosis is associated with an increased risk of cardiovascular events in respect to the non diabetic population. Hyperglycemia PER SE and associated with diabetes is an important risk factor for atherosclerosis. At present a substantial part of children with diabetes do not reach satisfactory glycemic control. Other risk factors for the development and progression of atherosclerosis may be inherited or develop in the course of the disease: hypertension, dyslipidemia, insulin resistance, obesity, cigarette smoking, physical inactivity, disturbance of platelet function, coagulation and fibrinolysis. The development and progression of atherosclerosis should be blocked at an early age, if possible. Primary prevention to all risk factors for cardiovascular disease is important and intervention is indicated if necessary. At the moment the best therapeutic strategy is to maintain metabolic control at a physiologic level and perform screening and early intervention for vascular complications.     

Mitochondrial Optic Neuropathies: How Two Genomes may Kill the Same Cell Type?

Ocular involvement is a prevalent feature in mitochondrial diseases. Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are both non-syndromic optic neuropathies with a mitochondrial etiology. LHON is associated with point mutations in the mitochondrial DNA (mtDNA), which affect subunit genes of complex I. The majority of DOA patients harbor mutations in the nuclear-encoded protein OPA1, which is targeted to mitochondria and participates to cristae organization and mitochondrial network dynamics. In both disorders the retinal ganglion cells (RGCs) are specific cellular targets of the degenerative process. We here review the clinical features and the genetic bases, and delineate the possible common pathomechanism for both these disorders.