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Elevation of cytosolic free Ca2+ inhibits the type VI adenylyl cyclase that predominates in C6-2B cells. However, it is not known whether there is any selective requirement for Ca2+ entry or release for inhibition of cAMP accumulation to occur. In the present study, the effectiveness of intracellular Ca2+ release evoked by three independent methods (thapsigargin, ionomycin, and UTP) was compared with the capacitative Ca2+ entry that was triggered by these treatments. In each situation, only Ca2+ entry could inhibit cAMP accumulation (La3+ ions blocked the effect); Ca2+ release, which was substantial in some cases, was without effect. A moderate inhibition, as was elicited by a modest degree of Ca2+ entry, could be rendered substantial in the absence of phosphodiesterase inhibitors. Such conditions more closely mimic the physiological situation of normal cells. These results are particularly significant, in demonstrating not only that Ca2+ entry mediates the inhibitory effects of Ca2+ on cAMP accumulation, but also that diffuse elevations in [Ca2+]i are ineffective in modulating cAMP synthesis. This property suggests that, as with certain Ca(2+)-sensitive ion channels, Ca(2+)-sensitive adenylyl cyclases may be functionally colocalized with Ca2+ entry channels.

A number of the currently described adenylyl cyclase species can be regulated by Ca2+ in the submicromolar concentration range in in vitro assays. The regulatory significance of these observations hinges on whether a physiological elevation in intracellular Ca2+ can regulate these cyclase activities in intact cells. However, achieving a physiological elevation in cytosolic Ca2+ is complicated by the fact that hormonal increases in cytosolic Ca2+ can be accompanied by additional effects, such as liberation of beta gamma-subunits of G-proteins and activation of protein kinase C, which can have disparate type-specific effects on cyclase activities. Therefore we have devised a strategy based on capacitative Ca2+ entry to show that, when types I and VI adenylyl cyclase are expressed in human embryonic kidney 293 cells, they are stimulated and inhibited respectively by Ca2+ entry. Blockade of Ca2+ entry by La3+ ions blocks the effects of Ca2+ entry on cyclic AMP synthesis. These studies establish that adenylyl cyclases deemed to be sensitive to Ca2+ in in vitro assays can be regulated by physiological Ca2+ entry, and therefore, such cyclases are poised to respond to changes in intracellular Ca2+ in tissues in which they are expressed.

Context:The outcome of patients with depressed fracture varies and depends on multiple factors. There has been no previous study on the significance of these factors on the outcome of depressed fracture of the skull and hence this study. Aims: The primary aim of our study is to find the factors affecting the outcome in cases of depressed skull fracture (DSF). This will help us improve outcomes and give more accurate prediction of long-term outcomes.Settings and Design:Prospective observational study.Subjects and Methods:Institutional Ethics Committee approval was taken for doing this observational study. This was conducted in a tertiary care institute by collecting data of fifty cases of DSFs in 2 years, between January 2012 and December 2013. The study included patients who were diagnosed with DSFs admitted to our tertiary care public hospital. Patients with comorbidity involving injury to other organs or medical disorders and pediatric patients were excluded from our study.Statistical Analysis Used:Chi-square test and Fisher exact test. Results: There was a statistically significant impact on age, sex, Glasgow Coma Scale (GCS) score at presentation, type of DSF, and site of DSF in the long-term outcome of patients. The patients with GCS score of 13 or more fared well with good long-term outcome as against those with GCS score below it. Any additional brain injury in the form of hematomas, etc., has a significant negative impact on long-term outcome of the patient and warrant urgent surgical intervention. Complications such as dural tear, cerebral contusions, wound infections, and seizures have adverse effect on the recovery.Conclusions:Our observation suggests that patients brought to hospital with minimal delay, with GCS score between 13 and 15, with simple DSF and normal brain parenchyma without dural tear, have the best outcome.

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