RAR-Related Orphan Receptor Gamma T (RoRγt)-Related Cytokines Play a Role in Neutrophil Infiltration of the Central Nervous System After Subarachnoid Hemorrhage

Neurocritical Care - How inflammatory cells are recruited into the central nervous system is a topic of interest in a number of neurological injuries. In aneurysmal subarachnoid hemorrhage (SAH),...     

Pulmonary pathologies in pallid mice result from nonhematopoietic defects

Several single gene pigment mutants of inbred C57BL/6J mice display a triad of subcellular granule-associated defects: oculocutaneous pigment dilution, prolonged bleeding due to defects in platelet dense granules, and abnormal lysosomes. These features also characterize Hermansky-Pudlak Syndrome (HPS), making these mice relevant animal models for HPS. Mice of one mutant strain, pallid, in addition to the hallmark triad of signs, also exhibit age-dependent lung pathology. Respiratory system mechanics showed that the age-dependent histopathology of pallid mice was accompanied by a decrease in lung reactance. Furthermore, the possibility that pallid pulmonary pathology may result from persistent inflammation due to microhemorrhage owing to the platelet defect was examined. Hematopoietic reconstitution of pallid mice with marrow from normal C57BL/6J donors did not prevent the development of the pulmonary histopathology or respiratory system mechanics characteristic of the pallid genotype. Similarly, wild-type mice 12 months after engraftment with pallid marrow did not develop pallid-like pulmonary histopathology or respiratory system mechanics. Thus, pallid-associated pulmonary functional and structural pathologies are not linked to the marrow (bleeding) genotype, but instead are the result of an age-dependent process resulting from a defect(s) in one or more nonhematopoietic cell types.     

Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination

This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination (IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/ IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly influence pregnancy rates with HMG/IUI therapy.      

Rat myometrial smooth muscle cells express endothelial nitric oxide synthase

We examined if rat myometrial cells in culture generate nitric oxide (NO) and express various isoforms of NO synthase (NOS). Myometrial cells isolated from rats on day 18 of gestation were incubated with various stimulators and inhibitors of NOS for 24 and 48 h, and NO production was evaluated by measuring nitrites in the media and NOS proteins in the cell lysates. NO was produced by myometrial cells and its production inhibited by N(G)-methyl-L-arginine (L-NMMA). This inhibition was reversed by L-arginine (3 mM). Interleukin-1beta (IL- 1beta) significantly stimulated NO production, in a dose-dependent manner. The IL-1beta-stimulated NO production was inhibited by the NOS inhibitor, L-NMMA, whose effects were reversed by L-arginine. Abundant NOS III protein was detectable in freshly isolated myometrial cells, and this was maintained in culture in the presence of fetal bovine serum (FBS; 10%). In the absence of FBS, NOS III levels decreased significantly (by 90%) within 24 h. In contrast, NOS I and NOS II proteins were undetectable in freshly isolated muscle cells and in cells cultured without IL-1beta. However, NOS II protein in these cells was induced by IL-1beta. Thus, NO is produced by myometrial cells through the NOS III isoform, and the myometrial NO may be important in maintaining uterine quiescence during pregnancy.      

Modeling of longitudinal academic achievement scores after pediatric traumatic brain injury

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.     

Health-related quality of life using the SF-36 in patients with bipolar disorder compared with patients with chronic back pain and the general population

BACKGROUND: The purpose of this study was to assess and compare the health-related quality of life of patients with bipolar disorder and chronic back pain and, in turn, to compare these results with those previously generated for the general population. METHODS: Subjects were patients with bipolar disorder (n=44), a comparison group of chronic back pain patients (n=30), and a population-based control sample (n=2,474). Health-related quality of life was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), a self-administered questionnaire in which lower scores are indicative of greater impairment. RESULTS: Patients with bipolar disorder had lower mean scores than the general population on all scales except Physical Functioning. Bipolar patients had significantly higher scores than chronic back pain patients in the categories of Physical Functioning, Role Limitations--Physical, Bodily Pain, and Social Function. There were no significant differences between bipolar disorder and chronic back pain groups in the Mental Health and Role Limitations - Emotional categories. LIMITATIONS: The results of the study are limited by the relatively small sample sizes of the bipolar and back pain patient groups. CONCLUSIONS: Patients with bipolar disorder had substantial impairment in health-related quality of life in comparison with the general population. Bipolar patients were less compromised in areas of physical and social functioning than chronic back pain patients but had similar impairment in mental health.     

Pharmacological antagonism of tyrosine kinases and MAP kinase in brainstem blocks taste aversion learning in mice

Although c-Fos induction in the brainstem is a reliable correlate of taste aversion learning and appears necessary for the encoding of the unconditioned stimulus, little is known about the intracellular signaling pathways in the brainstem that regulate c-Fos expression during taste aversion learning. Infusion of the tyrosine kinase inhibitor genistein and the MAP kinase kinase (MEK) inhibitor PD98059 into the fourth ventricle of mice potently blocks acquisition of a learned taste aversion. The unconditioned stimulus LiCl produces a rapid and robust phosphorylation of MAP kinase, as revealed by immunohistochemistry with an antibody specific to the dually phosphorylated active form of MAP kinase. This immunoreactivity is localized to the same region of the intermediate nucleus tractus solitarius in which we have shown large increases in c-Fos immunoreactive cells, suggesting that in at least a subset of these cells, MAP kinase activation may lead to c-fos induction.     

Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.