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Journal Article 2008; 29(4): 577-580 PubMed PMID: 18766159 Citation  Keywords:  Animals, Cochlea:metabolism, Ear, Inner:anatomy & histology, Homeostasis, Mice, RNA, Messenger:metabolism, Rats, Receptors, Atrial Natriuretic Factor:genetics, Stria Vascularis:metabolism, Vestibule, Labyrinth:metabolism,.   

OBJECTIVES: To examine whether the atrial natriuretic peptide receptor (NPR-A) is present in the secretory regions of the membrane labyrinth of the adult mouse inner ear.

SETTING: Recent studies have implied that the homeostasis of endolymph fluid in the inner ear may be regulated by receptor-mediated mechanisms. Several studies have identified the presence of atrial natriuretic peptide receptors in the inner ear of guinea pig and rat. As a member of the natriuretic peptide receptor family, which also includes B-type natriuretic peptide receptor (NPR-B) and C-type natriuretic peptide receptor (NPR-C), NPR-A may be involved in the regulation of fluid homeostasis in the inner ear.

METHODS: In this study, samples of stria vascularis, nonstrial tissue of the cochlear lateral wall and vestibular organ tissue from the ears of 6 adult mice were obtained by immediate excision of bony labyrinth under operating microscope after decapitation. Total RNA was isolated and mRNA was amplified by the reverse transcription-polymerase chain reaction (RT-PCR) using consensus primers flanking a region of 127 bp at the target sequence. Mouse renal cortex known to contain NPR-A was used as a positive control.

RESULTS: We demonstrated that NPR-A was expressed in the mouse stria vascularis as well as in the nonstrial tissue of the cochlear lateral wall and vestibular organ.

CONCLUSION: These results suggest that natriuretic peptides may play an important role in maintaining the fluid homeostasis of inner ear endolymph via interaction with NPR-A....

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Journal Article 2008; 29(4): 438-442 PubMed PMID: 18766153 Citation  Keywords:  Animals, Antibodies, Monoclonal:metabolism, Cerebral Ventricles:anatomy & histology, Choroid Plexus:cytology, Epithelial Cells:cytology, Female, Flow Cytometry, P-Glycoprotein:metabolism, Sheep,.   

OBJECTIVES: Previous studies in the female sheep have shown that photoperiod modulates the passage of sex steroids between the blood and the cerebrospinal fluid (CSF) and have suggested the involvement of efflux transport. The objective of the present work was to assess the presence of P-glycoprotein (Pgp), which could be responsible for this transport at the level of the choroid plexuses (CP).

METHODS: We used flow cytometry and the UIC2 monoclonal antibody against Pgp, to demonstrate the presence of Pgp in the epithelial cell fraction isolated from the sheep choroid plexuses (CPEC). Thanks to the size of the brain structures in sheep, we analyse separately the CP from 4th ventricle (4V) and the CP from the lateral ventricle (LV).

RESULTS: In the whole population isolated from the CP, the 4V contained a higher percentage of living, epithelial cells than the LV. The immunoreactive cells to the UIC2 antibody i.e. bearing activated form of Pgp, represented 26.8% of the CPEC in the 4V, and 39.3% in the LV (P<0.05).

CONCLUSION: Pgp is expressed in the CPEC from the sheep. Differences in the expression of Pgp between CPEC from LV and 4V might suggest in vivo functional differences between LV and 4V CP in sheep....

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Journal Article 2008; 29(4): 467-474 PubMed PMID: 18766152 Citation  Keywords:  Affect:physiology, Aged, Amygdala:anatomy & histology, Cerebral Cortex:anatomy & histology, Cognition:physiology, Estrogens:blood, Female, Fluorodeoxyglucose F18:metabolism, Humans, Menopause:physiology, Middle Aged, Nerve Net:physiology, Positron-Emissio.   

OBJECTIVES: 1.) Expand the scope of neuroendocrine applications of functional neuroimaging techniques. 2.) Compare the covariance of amygdalar activity with that of the rest of the brain during pre- and post-menopausal levels of estrogen (E2). Based on the distribution of cortical E2 receptors and the neocortical regions where E2 has been shown to preferentially accumulate, we predict that E2 infusion will increase covariance of amygdalar activity with that of the temporal and frontal cortices.

DESIGN: This basic physiology study employed a within-subject design. All participants were post-menopausal women (n =7). Analysis of covariance between whole brain and amygdalar regional cerebral glucose consumption (CMRglc) was conducted in a voxel-wise manner by means of the basic regression option in SPM2 and was applied to FDG-PET scans acquired at baseline and after a 24 hour graded E2 infusion.

SETTING: An academic medical center; Massachusetts General Hospital, Boston, Massachusetts.

RESULTS: E2 levels (mean +/- sem) were significantly greater at 24 hours (257.9 pg/mL +/- 29.7) than at 0 hours (28.1 pg/mL +/- 3.4). Right amygdalar CMRglc showed a significant covariance with activity of three different regions of the temporal cortex during E2 infusion, but none at baseline. In addition, right amygdalar CMRglc covaried with that of the right medial and superior frontal gyri only during E2 infusion.

CONCLUSIONS: In addition to suggesting changes in amygdalar-cortical network connectivity as a result of short-term E2 exposure, these analyses provide evidence that basic neuroendocrine research may benefit from further use of FDG-PET and other functional neuroimaging modalities for network level analyses....

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Journal Article 2008; 29(4): 475-481 PubMed PMID: 18766148 Citation  Keywords:  Adult, Animals, Female, Humans, Infant, Newborn, Male, Neuroprotective Agents:metabolism, Reaction Time:physiology, Rh-Hr Blood-Group System:metabolism, Testosterone:blood, Toxoplasma:metabolism, Toxoplasmosis:physiopathology,.   

BACKGROUND: The biological function of RhD protein, a major component of the Rh blood group system, is largely unknown. No phenotypic effect of RhD protein, except its role in hemolytic disease of newborns and protective role against Toxoplasma-induced impairment of reaction times in men, has been described.

METHODS: Here we searched for a protective effect of RhD positivity against Toxoplasma-induced prolongation of reaction times in a set of 110 male and 226 female students of the Faculty of Science tested for latent toxoplasmosis and concentration of testosterone in saliva.

RESULTS: RhD-positive subjects have been confirmed to be less sensitive to the influence of latent toxoplasmosis on reaction times than Rh-negative subjects. While a protective role of RhD positivity has been demonstrated previously in four populations of men, the present study has shown a similar effect in 226 female students. Our results have also shown that the concentration of testosterone in saliva strongly influences (reduces) reaction times (especially in men) and therefore, this factor should be controlled in future reaction times studies.

CONCLUSIONS: The observed effects of RhD phenotype could provide not only a clue to the long-standing evolutionary enigma of the origin of RhD polymorphism in humans (the effect of balancing selection), differences in the RhD+ allele frequencies in geographically distinct populations (resulting from geographic variation in the prevalence of Toxoplasma gondii), but might also be the missing piece in the puzzle of the physiological function of the RhD molecule....

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Journal Article 2008; 29(4): 454-460 PubMed PMID: 18766144 Citation  Keywords:  Adult, Aged, Biomechanical Phenomena, Elasticity, Female, Humans, Middle Aged, Models, Theoretical, Myometrium:anatomy & histology, Rheology, Stress, Mechanical,.   

: This work answers some questions related to detection of rheological properties of soft tissues exemplified in myometrium, stressed by external tensile force. In the first stage of the experiment the tissue samples were ciclically stressed and response loops were recorded. This test proved severe plastical deformation of samples, which is not usually being stated for living tissues. In addition to course, growth and stabilizing this deformation also energetical losses of individual hysteresis loops of the response were evaluated. In the second stage of the experiment the tissue samples were exposed to a loading force changed in step-wise manner in four steps. The sample response to each force step was processed and evaluated separately to obtain basic properties of used model. In next step, the changes in model characteristics were obtained and evaluated for each element in subsequent force steps. By reason of following easier interpretation, the quite simple visco-elastic model, defined by differential equation with analytic solution, is used. The results prove necessary to introduce in model both spring and damper constants dependent on the magnitude of the loading force and one damper with even time dependent constant. The interindividual variability of characteristic values of the model elements is surprisingly low. On the other side, they are strongly dependent on load magnitude. Complete mathematical model of uterine wall tissue is obtained by amending the principal equation by formulas describing changes in individual components of the model....

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Journal Article 2008; 29(4): 443-446 PubMed PMID: 18766141 Citation  Keywords:  Adult, Aged, Antigens, CD34:analysis, Breast Neoplasms:blood supply, Carcinoma, Ductal, Breast:blood supply, Female, Humans, Immunohistochemistry, Lymph Nodes:metabolism, Lymphatic Metastasis:pathology, Middle Aged, Neoplasm Invasiveness, Neovascularizati.   

BACKGROUND: Angiogenesis is a basic process that enables neoplasms to thrive. Microvessel density (MVD) evaluation is an accepted parameter for assessing the angiogenesis process within a tumor. The aim of the present study has been to assess the number of microcapillaries in both invasive ductal breast cancer with the presence of metastases in regional lymph nodes and in invasive ductal breast cancer without such metastases.

METHODS: The CD34 antigen immunoreactivity level was assessed by immunohistochemistry in both types of invasive ductal breast cancer. Tissue samples were obtained from 40 patients and were divided into two groups according to whether or not there were lymph node metastases.

RESULTS: The patients with lymph node metastases exhibited statistically significantly higher numbers of stained microcapillaries than the patients who did not have lymph node metastases.

CONCLUSION: Thus the number of stained microcapillaries as evaluated by using the CD34 immunoreactivity level seems to be a useful predictor for the development of local lymph node metastases in female invasive ductal breast cancer....

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Journal Article 2008; 29(4): 493-499 PubMed PMID: 18766139 Citation  Keywords:  Adult, Blood Flow Velocity, Deoxyribonucleases, Type II Site-Specific:genetics, Female, Fetal Growth Retardation:genetics, Fetus:anatomy & histology, Genotype, Gestational Age, Humans, Laser-Doppler Flowmetry, Middle Cerebral Artery, Polymorphism, Genetic.   

OBJECTIVES: The intrauterine growth restriction (IUGR) frequently is a cause of fetal morbidity and mortality, and influences perinatal outcome. Several genes have been identified to explain aetiology of IUGR, beside others the gene coding for tumour necrosis factor alpha (TNF-alpha).

DESIGN: To investigate frequency of AlwI polymorphism of TNF-alpha gene and its correlation with TNF-alpha level in maternal serum, Doppler velocimetry and perinatal outcome in pregnancies suspected for IUGR.

SETTING: 42 pregnancies with IUGR and 50 matched healthy pregnant women were included in the study. Maternal venous blood samples were investigated in relationship to blood flow Doppler velocimetry in umbilical (UA) and middle cerebral (MCA) arteries. AlwI polymorphism was analysed using PCR/RFLP assays. TNF-alpha level was evaluated by immunoelectophoretic method.

RESULTS: A higher frequency of mutated -238A alleles (13.1% vs. 7.0%) and genotypes containing at least one mutated -238A allele (23.8% vs. 14.0%) were found in the IUGR group. The tendency to the higher TNF-alpha level in IUGR subgroups with the presence of at least one mutated A allele (258.9+/-231.3 vs. 174.1+/-145.6 pg/ml) was detected. No statistical differences were detected for PI values in UA and MCA arteries considering particular genotypes (GG vs. GA + AA) separately in IUGR group.

CONCLUSION: Increased UA vascular impedance and signs of brain sparing in MCA are related to IUGR and increased TNF-alpha level in maternal serum. AlwI polymorphism might play a role in IUGR aetiology and influence TNF-alpha expression in maternal serum, but was not related to Doppler velocimetry or with perinatal outcome....

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Journal Article 2008; 29(3): 347-350 PubMed PMID: 18580839 Citation  Keywords:  ACTH-Secreting Pituitary Adenoma:metabolism, Adenoma:metabolism, Adrenocorticotropic Hormone:metabolism, Adult, Cushing Syndrome:blood, Female, Humans, Immunohistochemistry, Ki-67 Antigen:blood, Male, Nelson Syndrome:blood, Paraffin Embedding, Pituitary H.   

OBJECTIVES: The aim of the study was to evaluate the ACTH-immunopositive pituitary adenomas, especially those without manifestation of Cushing's disease

MATERIAL AND METHODS: 148 pituitary adenomas removed surgically in years 1994--2007 were studied. The paraffin sections were immunostained with antibodies against the pituitary hormones. In 79 adenomas the immunostaining with anti-ACTH antibody was performed Additionally, 23 tumors were also immunostained with anti-Ki-67 (MIB-1) antibody. Visualization of reactions was done by means of streptavidin-biotin-peroxidase technique with use of 3,3'-diaminobenzidine as chromogen.

RESULTS: ACTH immunopositivity was found in 34 cases (23%). Fourteen ACTH-immunopositive tumors manifested themselves as Cushing's disease (including 1 case of Nelson's syndrome). In the remaining 20 cases in spite of the positive immunostaining for ACTH of the tumor cells, no features of hypercortisolism were observed (in several cases even hypocortisolism was found). Thus, those tumors represented so-called "silent" corticotropinomas. Over one third (37%) of "clinically" nonfunctioning pituitary adenomas, when immunostained with anti-ACTH antibody, showed ACTH immunopositivity. Three adenomas in patients with Cushing's disease (21.4%) and 7 "silent" corticotropinomas (35%) were recurrent tumors. In contrast, the recurrence rate in the group of ACTH-immunonegative clinically nonfunctioning pituitary adenomas was 14.7%. The "silent" corticotropinomas exhibited a tendency towards the higher expression of a proliferation marker, Ki-67 antigen as compared to the "active" corticotropinomas.

CONCLUSIONS: (i) "Silent" corticotropinomas are rather frequent. (ii) This adenoma type should be considered as aggressive. (iii) It is hypothetized that--like in Nelson's syndrome--the lack of hypercortisolism or even presence of hypocortisolism favorizes the exaggerated growth of tumoral corticotrophs....

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