Dental and oral anomalies in incontinentia pigmenti: a systematic review

Objectives

Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a mutation of the IKBKG gene. The objective of this study was to present a systematic review of the dental and oral types of anomalies, to determine the total number and sex distribution of the anomalies, and to analyze possible therapies.

Materials and methods

We analyzed the literature data from 1,286 IP cases from the period 1993–2010.

Results

Dental and/or oral anomalies were diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types were dental, and the most frequent of these were dental shape anomalies, hypodontia, and delayed dentition. The most frequent oral anomaly types were cleft palate and high arched palate. IKBKG exon 4–10 deletion was present in 86.36% of genetically confirmed IP patients.

Conclusions

According to the frequency, dental and/or oral anomalies represent the most frequent and important IP minor criteria. The most frequent mutation was IKBKG exon 4–10 deletion. The majority of dental anomalies and some of the oral anomalies could be corrected.

Clinical relevance

Because of the presence of cleft palate and high arched palate in IP patients, these two anomalies may be considered as diagnostic IP minor criteria as well.     

Folliculo-stellate cells – Potential mediators of the inflammaging-induced hyperactivity of the hypothalamic–pituitary–adrenal axis in healthy elderly individuals

Some evidence has suggested that, with age, the hypothalamic–pituitary–adrenal (HPA) axis becomes less resilient, leading to higher glucocorticoids nocturnal levels and a flattening of the circadian profiles. Such age-related changes in the activity of the HPA axis has overexposed the brain and peripheral organs to the effects of the glucocorticoids, increasing the morbidity and mortality rates of the elderly. Debate among scientists regarding the contributions of HPA axis age-related changes of impaired feedback regulation vs. direct overactivation persists. Supporters of impaired feedback regulation assumed that this effect might be the consequence of the hippocampal age-related neuronal loss and the reduction of the number of mineralocorticoid and glucocorticoid receptors. On the other hand, healthy elderly individuals are characterized by an increase of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, and the development of a chronic low-grade inflammatory state, known as inflammaging. Cytokines central to inflammaging send signals to the brain, activate HPA axis, and, by increased cortisol secretion, down-regulate inflammaging in a process known as anti-inflammaging. Even as these cytokines act at the level of the hypothalamic paraventricular nucleus, they are hampered by the intact blood–brain barrier. Further, the corticotropes in the anterior pituitary do not express cytokine receptors, and the density of folliculo-stellate cells generally increases with age. Therefore, we assumed that folliculo-stellate cells were the target structures through which the elevated levels of cytokines, as a part of the inflammaging phenomenon, would cause the overactivation of the HPA axis in healthy elderly individuals. Folliculo-stellate cells are non-endocrine cells that were originally considered to act as supporting cells for the endocrine cells. Despite the fact that FS cells do not produce any of the established hormones of the anterior pituitary, they secrete paracrine agents that act locally to modulate pituitary responses to hypothalamic and peripheral signals. There is evidence of cytokines characteristically involved in inflammaging. For example, IL-1 and TNF-α are thought to stimulate folliculo-stellate cells to release various paracrine agents, including IL-6, IL-11, leukemia inhibitory factor, and macrophage migration inhibitory factor. Through different mechanisms, these agents induce ACTH release by corticotropes. Therefore, it can be concluded that folliculo-stellate cells may act as potent mediators of the age-related HPA axis hyperactivity induced by cytokines characteristic of the inflammaging phenomenon in healthy elderly individuals.     

Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling

Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell–astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca²⁺ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca²⁺ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca²⁺ increase is specifically triggered by the autoreactive CD4⁺ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca²⁺ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell–astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.     

Parahippocampal corpora amylacea and neuronal lipofuscin in human aging

The aim of this research was to quantify the number of corpora amylacea and lipofuscin-bearing neurons in the parahippocampal region of the brain. Right parahippocampal gyrus specimens of 30 cadavers were used as material for histological and morphometric analyses. A combined Alcian Blue and Periodic Acid-Schiff technique was used for identification and quantification of corpora amylacea and lipofuscin-bearing neurons. Immunohistochemistry was performed using S100 polyclonal, neuron-specific enolase and glial fibrillary acidic protein monoclonal antibodies for differentiation of corpora amylacea and other spherical inclusions of the aging brain. Cluster analysis of obtained data showed the presence of three age groups (median age: I = 41.5, II = 68, III = 71.5). The second group was characterized by a significantly higher numerical density of subcortical corpora amylacea and number of lipofuscin-bearing neurons than other two groups. Values of the latter cited parameters in the third group were insignificantly higher than the first younger group. Linear regression showed that number of parahippocampal lipofuscin-bearing neurons significantly predicts numerical density of subcortical corpora amylacea. The above results suggest that more numerous parahippocampal region corpora amylacea and lipofuscin-bearing neurons in some older cases might represent signs of its’ neurons quantitatively-altered metabolism.     

Frequent attenders in general practice: quality of life,patient satisfaction,use of medical services and GP characteristics

Objectives - To describe where patients in Danish general practice get information about health and disease, particularly how patients prepare for a visit to their GP, with special reference to use of the Internet. Design - Structured interviews. Setting - Four Danish general practices. Patients - 93 consecutive patients after visiting their GP. Main outcome measures - The patient's report about use of the Internet and different mass media in preparation for the consultation. Results - Only two patients never looked for health information. Of all patients, 20% had used the Internet to get health information, 8% because of the current visit, i.e. a third of all with Internet access had used it because of the current visit. Women used the sources of information more than men did. Personal contact with family, friends or neighbours was the most commonly used source. Conclusion - The Internet is used in direct preparation for a visit to the general practitioner. The vast majority of patients use the mass media for information. In general practice, the main source of information on a health-related subject is personal contact with family and friends.     

Coexistence of Unverricht-Lundborg disease and congenital deafness: Molecular resolution of a complex comorbidity

Purpose :  We report on genetic analysis of a complex condition in a Serbian family of four siblings, wherein two had progressive myoclonic epilepsy (PME) and congenital deafness (CD), one had isolated congenital deafness (ICD), and one was healthy.
Methods and Results :  Molecular diagnosis performed by Southern blotting confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In the sibling with ICD (heterozygote for expansion mutation in CSTB ) we demonstrated recombination event between the D21S2040 marker and the CSTB gene and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well.
Discussion :  To the best of our knowledge this is the first genetic confirmation of the coexistence of these two mutations.     

CXCL12 in control of neuroinflammation

Inflammation within the central nervous system (CNS) is strictly controlled and if possible prevented. Such a tight control is necessary due to high sensitivity of nervous tissue to mechanical and biochemical consequences of inflammation. Still, neuroinflammation is a typical feature of a chronic, inflammatory, demyelinating disease multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). It is assumed that mechanisms that should prevent activation of immune cells at the periphery, in the lymphoid tissues, and/or inflammation within the CNS are inadequately efficient in MS patients. Here, some recent data about the importance of CXCL12 for regulation of neuroinflammation and contribution of its deviant expression within the CNS to EAE and MS pathogenesis are presented.     

DMCM, a benzodiazepine site inverse agonist, improves active avoidance and motivation in the rat

There are several modulatory sites at GABA(A) receptors, which mediate the actions of many drugs, among them benzodiazepine. Three kinds of allosteric modulators act through the benzodiazepine binding site: positive (agonist), neutral (antagonist), and negative (inverse agonist). The goal of the present study was to examine the influence of the inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) acting on α GABA(A) receptor and compare its dose-response effects on memory and depression-like behavior. We independently studied the effects of DMCM (0.05-1.0mg/kg) on retention versus acquisition of active avoidance and depression-like behavior in the forced swim test. Throughout the study, drugs were given intraperitoneally, 30min before testing. ANOVA has showed that treatment with DMCM significantly affected retrieval of avoidance response (p<0.05), exerted promnesic effects in inverted U-shape manner. Dunnett's test indicated that the DMCM avoidance-facilitatory dose was 0.1mg/kg. At the dose facilitating retrieval of avoidance memory, DMCM significantly (p<0.05, comparison of regression coefficients by Student's t-test) and progressively increased acquisition rate during 5 days training, compared to the saline group. In forced swim test, ANOVA indicated statistically significant effects of DMCM (p<0.05). Dunnett's analysis showed that DMCM significantly decreased immobility time at the dose of 0.1mg/kg, exerted acute antidepressant-like effects. Our results experimentally support the findings that under certain circumstances, nonselective benzodiazepine site inverse agonists, produce memory-enhancing and antidepressant-like effects. The molecular and neuronal substrates linking the actions of specific GABA-benzodiazepine receptor complex subunits remains to be further elucidated.     

DNA profiling of B chromosomes from the yellow-necked mouse Apodemus flavicollis (Rodentia, Mammalia)

Using AP-PCR-based DNA profiling we examined some structural features of B chromosomes from yellow-necked mice Apodemus flavicollis. Mice harboring one, two, or three or lacking B chromosomes were examined. Chromosomal structure was scanned for variant bands by using a series of arbitrary primers and from these, informative bands were selected. The selection criteria used were the ability to differentiate between individuals of the species, to detect markers common for both A and B chromosomes, and, importantly, to differentiate between A- and B-chromosome sets. In addition to primers, profiling conditions were found to be critical for meeting the selection criteria. Primers and analysis conditions that demonstrated structural characteristics unique to the B-chromosome set are described. These characteristics included variant bands as qualitative parameters and altered electrophoretic band intensities as quantitative distinctions estimated by integration of densitometric profiles of electrophoretograms. B chromosome-specific molecular markers are easy to detect by AP-PCR-based DNA profiling in the presence of a full set of A chromosomes. Models for the origin of yellow-necked mouse B chromosomes are discussed in the context of presented data.