Cabergoline therapy for macroprolactinoma during pregnancy: a case report.

Background: We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine. Case presentation: We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval of breastfeeding. At 37 weeks of gestation, the patient delivered a healthy baby. Conclusion: We were able to safely treat macroprolactinemia in our patient during pregnancy with cabergoline. This case report contributes to the relatively meager data available which advocates the safety of cabergoline therapy in pregnant hyperprolactinemic patients

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Lateralization in the Invertebrate Brain: Left-Right Asymmetry of Olfaction in Bumble Bee, Bombus terrestris

Brain and behavioural lateralization at the population level has been recently hypothesized to have evolved under social selective pressures as a strategy to optimize coordination among asymmetrical individuals. Evidence for this hypothesis have been collected in Hymenoptera: eusocial honey bees showed olfactory lateralization at the population level, whereas solitary mason bees only showed individual-level olfactory lateralization. Here we investigated lateralization of odour detection and learning in the bumble bee, Bombus terrestris L., an annual eusocial species of Hymenoptera. By training bumble bees on the proboscis extension reflex paradigm with only one antenna in use, we provided the very first evidence of asymmetrical performance favouring the right antenna in responding to learned odours in this species. Electroantennographic responses did not reveal significant antennal asymmetries in odour detection, whereas morphological counting of olfactory sensilla showed a predominance in the number of olfactory sensilla trichodea type A in the right antenna. The occurrence of a population level asymmetry in olfactory learning of bumble bee provides new information on the relationship between social behaviour and the evolution of population-level asymmetries in animals

Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

<p>Abstract</p> <p>Background</p> <p>Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot.</p> <p>Methods</p> <p>We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects.</p> <p>Results</p> <p>We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, <it>p </it>= 0.017 and Notch, <it>p </it>= 0.003) appeared to be generally suppressed.</p> <p>Conclusions</p> <p>The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.</p

Cloacal Bacterial Diversity Increases with Multiple Mates: Evidence of Sexual Transmission in Female Common Lizards

Sexually transmitted diseases have often been suggested as a potential cost of multiple mating and as playing a major role in the evolution of mating systems. Yet there is little empirical data relating mating strategies to sexually transmitted microorganisms in wild populations. We investigated whether mating behaviour influences the diversity and composition of cloacal assemblages by comparing bacterial communities in the cloaca of monandrous and polyandrous female common lizards Zootoca vivipara sampled after the mating period. We found that polyandrous females harboured more diverse communities and differed more in community composition than did monandrous females. Furthermore, cloacal diversity and variability were found to decrease with age in polyandrous females. Our results suggest that the higher bacterial diversity found in polyandrous females is due to the sexual transmission of bacteria by multiple mates. The impact of mating behaviour on the cloacal microbiota may have fitness consequences for females and may comprise a selective pressure shaping the evolution of mating systems

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A&gt;G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A&gt;G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Hydrogen Peroxide Acts on Sensitive Mitochondrial Proteins to Induce Death of a Fungal Pathogen Revealed by Proteomic Analysis

How the host cells of plants and animals protect themselves against fungal invasion is a biologically interesting and economically important problem. Here we investigate the mechanistic process that leads to death of Penicillium expansum, a widespread phytopathogenic fungus, by identifying the cellular compounds affected by hydrogen peroxide (H2O2) that is frequently produced as a response of the host cells. We show that plasma membrane damage was not the main reason for H2O2-induced death of the fungal pathogen. Proteomic analysis of the changes of total cellular proteins in P. expansum showed that a large proportion of the differentially expressed proteins appeared to be of mitochondrial origin, implying that mitochondria may be involved in this process. We then performed mitochondrial sub-proteomic analysis to seek the H2O2-sensitive proteins in P. expansum. A set of mitochondrial proteins were identified, including respiratory chain complexes I and III, F1F0 ATP synthase, and mitochondrial phosphate carrier protein. The functions of several proteins were further investigated to determine their effects on the H2O2-induced fungal death. Through fluorescent co-localization and the use of specific inhibitor, we provide evidence that complex III of the mitochondrial respiratory chain contributes to ROS generation in fungal mitochondria under H2O2 stress. The undesirable accumulation of ROS caused oxidative damage of mitochondrial proteins and led to the collapse of mitochondrial membrane potential. Meanwhile, we demonstrate that ATP synthase is involved in the response of fungal pathogen to oxidative stress, because inhibition of ATP synthase by oligomycin decreases survival. Our data suggest that mitochondrial impairment due to functional alteration of oxidative stress-sensitive proteins is associated with fungal death caused by H2O2

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.