Inhibition of ovarian steroidogenesis by cyclic GMP in a fly

Previous investigations in the female blowfly Phormia regina have shown that 3-isobutyl-1-methylxanthine (IBMX), a broad spectrum inhibitor of phosphodiesterases (PDEs), fails to mimic the steroidogenic effects of cAMP on ovaries, although it efficiently increases the concentrations of this second messenger. In this study, experiments carried out to clear up this contradiction demonstrated that IBMX, besides its effect on cAMP, also increased cGMP concentrations in blowfly ovary and that these two cyclic nucleotides controlled ovarian steroidogenesis antagonistically. In particular, a selective inhibitor of cGMP-specific PDEs, unlike IBMX, had a very strong negative effect on ovarian steroidogenesis. Moreover, a cGMP analog was able to inhibit steroid biosynthesis in previtellogenic and vitellogenic ovaries, thus affecting basal and acute steroidogenesis respectively. Our observations also demonstrated that cGMP was always present in blowfly ovary, reaching its maximal levels at the end of vitellogenesis, in close correlation with the physiological decrease in ovarian steroidogenesis. Experiments using an inhibitor of protein kinase G clearly indicated that the effects of cGMP were mediated by this enzyme. On the contrary, these effects did not seem to involve cGMP-regulated PDEs or ion channels. Our results also indicated that ovarian cGMP concentrations were not controlled by brain factors, suggesting a probable involvement of paracrine/autocrine factors. Nitric oxide (NO) appeared to be a good candidate for such a control, because an NO donor was able to stimulate ovarian cGMP concentrations and to drastically decrease ovarian ecdysteroid biosynthesis in blowflies. These data thus demonstrate, for the first time in invertebrates, a potent role of cGMP in the negative control of ovarian steroidogenesis and suggest a possible co-regulation with NO.     

Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study

OBJECTIVE: Velocardiofacial syndrome, caused by a deletion on chromosome 22q11.2, is often accompanied by cognitive, behavioral, and psychiatric impairments. Specifically, velocardiofacial syndrome has been proposed as a disease model for a genetically mediated subtype of schizophrenia. Velocardiofacial syndrome is also known to affect brain structure. The most prominent structural findings in velocardiofacial syndrome are reduced white matter volumes. However, the structure of white matter and extent of specific regional involvement in this syndrome have never been investigated. The current study used diffusion tensor imaging to investigate white matter structure in children and young adults with velocardiofacial syndrome. METHOD: Nineteen participants with velocardiofacial syndrome and 19 age- and gender-matched comparison subjects underwent diffusion-weighted magnetic resonance imaging scans. Whole brain voxel-by-voxel analyses were conducted to investigate white matter fractional anisotropy differences between the groups. RESULTS: Relative to the comparison group, the velocardiofacial syndrome group had reduced white matter anisotropy in the frontal, parietal, and temporal regions as well as in tracts connecting the frontal and temporal lobes. CONCLUSIONS: This study demonstrates that alterations of white matter tract structure occur in velocardiofacial syndrome. Reduced white matter anisotropy was observed in individuals with velocardiofacial syndrome in areas previously implicated in the neurocognitive phenotype of velocardiofacial syndrome. The finding of aberrant parietal white matter tracts as well as aberrant frontotemporal connectivity in velocardiofacial syndrome and in previous schizophrenia studies may be associated with increased vulnerability for development of psychotic symptoms.     

IL-1 beta is a better inducer of apoptosis in human fetal membranes than IL-6

The objective of this study was to compare two of the inflammatory cytokines (IL-1 and IL-6) elevated in both preterm labour and preterm premature rupture of the membranes (pPROM), with respect to their ability to induce fetal membrane apoptosis. Fetal membranes collected from women at term were placed in an organ explant system and stimulated with recombinant human IL-1 beta and IL-6. The expression patterns of pro-apoptotic genes (Fas, FasL, TRADD, FADD) and caspases 2, 3, 8, 9 were studied using PCR. Caspase activity and DNA fragmentation were studied using substrate assays and TUNEL respectively. Caspase 8 and 9 expressions were induced in IL-1 beta and IL-6 treated amniochorion. Caspase 2 expression was seen only in IL-1 beta stimulated tissues. When compared to control, IL-1 beta increased caspase 2, 3, 8 and 9 activities, whereas IL-6 treated membranes did not exhibit a significant change. DNA fragmentation was seen in greater numbers after IL-1 beta treatment than after IL-6 treatment. This study demonstrates that IL-1 beta is a better inducer of apoptosis in normal human fetal membranes than IL-6.     

Thoracoscopic repair of eventration of diaphragm

pen thoracotomy and plication of eventration of diaphragm leads to hypoventilation due to pain and lung contusion due to retraction. We present two cases, 8 month and 4 years old; in whom plication was done thoracoscopically. Both had smooth recovery, early extubation and excellent cosmetic result.