Cerebral blood flow velocity after mannitol infusion in children

Purpose

There is conflicting evidence as to whether the effect of mannitol on brain bulk arises from haemodynamic, rheologic, or osmotic mechanisms. If mannitol alters cerebral haemodynamics by inducing vasoconstriction, this change should be reflected in cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA). The purpose of this study was to evaluate the effect of mannitol on CBFV in children.

Methods

Children scheduled for intracranial surgery were enrolled. After a loading dose of 10 μg · kg^?1 of fentanyl, general anaesthesia was maintained with fentanyl (3 μg · kg^?1 · hr^?1), 66% nitrous oxide, and isoflurane (0.2–0.5% inspired). Mean and systolic CBFV (Vm and Vs) and pulsatility index (PI) were recorded with a transcranial Doppler (TCD) directed at the M1 segment of the MCA. Mannitol was administered, 1 gm · kg^?1 iv over 15 min. The osmolality (Osm), haematocrit (Hct), mean arterial pressure (MAP), heart rate (HR), and TCD variables were recorded before and 15, 30, 45, and 60 min after the mannitol infusion.

Results

Mannitol infusion resulted in an increase in Osm and decrease in Hct (P < 0.05). Heart rate, MAP and arterial carbon dioxide tensions did not change (P > 0.05) during the measuring period. The Vm did not vary from baseline. The Vs and P1 both increased briefly (P < 0.01 at 15 min and P < 0.05 at 30 min) after the mannitol, suggesting an increase in resistance distal to the MCA.

Conclusion

The time course of CBFV changes produced by mannitol corresponds with previous animal data concerning cerebrovascular tone. Our results suggest that mannitol briefly increases cerebrovascular resistance and thereby diminishes cerebral blood volume.     

Voluntary sucrose ingestion, like corticosterone replacement, prevents the metabolic deficits of adrenalectomy

We tested whether corticosterone replacement causes increased sucrose drinking in adrenalectomized (ADX) rats compared to sham-ADX (sham) rats. ADX rats given high doses of corticosterone drank as much sucrose as sham rats, whereas at three lower doses of corticosterone, drinking was similar between groups and was only approximately 40% of that ingested by shams. Compared to sham rats, ADX rats drinking saline, or saline and saccharin, gain weight more slowly, contain less white adipose tissue, and have higher sympathetic outflow as assessed by uncoupling protein content in brown adipose tissue. Allowing sucrose as well as saline to drink restored all of these variables to normal in ADX rats with no- or low-corticosterone. All endpoints from sucrose-drinking ADX rats with no-or low-corticosterone were indistinguishable from those in water-drinking shams. By contrast, sucrose-drinking ADX rats that were given high doses of corticosterone exhibited the usual catabolic effects of corticosterone on body weight gain and, unlike sucrose-drinking shams, were obese. We conclude that (i) high corticosterone stimulates the potability of sucrose and inhibits sympathetic stimulation of uncoupling protein; (ii) sucrose, without corticosterone, normalizes metabolic deficits in ADX rats probably through actions mediated both peripherally and by the central nervous system; and (iii) ADX rats have a distinct sucrose appetite.     

Spontaneous uterine rupture in a patient with polyhydramnios as only risk factor. Case report, literature review and institutional experience

The uterine rupture is a catastrophic obstetric complication. The main risk factor is an antecedent of uterine surgery, usually caesarean. It is reported the case of a 39-years-old patient with 37 week-pregnancy and polyhydramnios, without surgical antecedents, whose was not in labor and developed complete rupture of the lateral face of the uterus, which was spontaneous, without previous uterine scar and with a unusual outcome.     

Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride

BACKGROUND: Efficiency of engraftment after liver cell transplantation is less than 1% under conventional conditions. Our aim was to develop a high-efficiency, nonsurgical, no-genetic-advantage mouse model of liver repopulation with transplanted cells. METHODS: Mice were conditioned with nonlethal doses of a cell cycle inhibitor, retrorsine, 70 mg/kg, to irreversibly block proliferation of native hepatocytes. After the drug was eliminated, 2 million freshly isolated beta-galactosidase-labeled liver cells were transplanted into the spleens of C57BL/6J recipient mice. To stimulate donor cell proliferation, three doses of carbon tetrachloride (CCl4), 0.5 ml/kg, were given. Several control groups were studied to evaluate the contribution of each treatment to liver repopulation. RESULTS: Repopulation, as measured by cell isolation from recipient livers 1-7 months after transplantation, was on average 20%. Repopulation was 10% if CCl4 was given only once, between 0.5% and 1% if only retrorsine or CCl4 were used, and 0.05% if no conditioning was used. Phenotypically, whole livers turned blue on exposure to X-gal staining, whereas negative (control) livers remained pale brown. More than 55% of liver repopulation resulted from clusters containing 21 or more cells, some of which contained more than 200 cells, suggesting seven or more rounds of cell division in a subset of transplanted cells. CONCLUSION: This murine study demonstrates high levels of repopulation after liver cell transplantation into nongenetically modified livers, using a cell cycle inhibitor and chemical liver injury to provide transplanted cells a proliferative advantage. Liver repopulation was effected mostly by a small fraction of transplanted cells. Analogous nonsurgical liver cell transplantation strategies, but with clinically applicable drugs, could be devised for the treatment of liver-based metabolic diseases.     

Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury

OBJECTIVE: To investigate the effects of inosine on the acute lung inflammation induced by lipopolysaccharide (LPS) in vivo and on the activation and cytotoxicity elicited by proinflammatory cytokines on human lung epithelial (A549) cells in vitro. SUMMARY BACKGROUND DATA: Inosine is an endogenous purine recently shown to exert immunomodulatory and antiinflammatory effects. METHODS: Mice challenged with intratracheal LPS (50 microg) were treated after 1, 6, and 12 hours with inosine (200 mg/kg intraperitoneal) or vehicle. After 24 hours, bronchoalveolar lavage fluid was obtained to measure proinflammatory (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, IL-6), and antiinflammatory (IL-10, IL-4) cytokines, chemokines (MIP-1alpha and MIP-2), myeloperoxidase activity and total cell counts, nitric oxide production, and proteins. Lung histology and immunohistochemical detection of 3-nitrotyrosine, a marker of nitrosative stress, were performed in inflated-fixed lungs. In vitro, cell viability and production of the chemokine IL-8 were evaluated in A549 cells stimulated with a mixture of cytokines in the presence or absence of inosine. RESULTS: Inosine downregulated the LPS-induced expression of TNF-alpha, IL-1beta, IL-6 and MIP-2 and tended to reduce MIP-1alpha, whereas it enhanced the production of IL-4. Total leukocyte counts, myeloperoxidase, nitric oxide production, and proteins were all significantly decreased by inosine. The purine also improved lung morphology and suppressed 3-nitrotyrosine staining in the lungs after LPS. Inosine attenuated the cytotoxicity and the expression of IL-8 induced by proinflammatory cytokines in A549 cells. CONCLUSIONS: Inosine largely suppressed LPS-induced lung inflammation in vivo and reduced the toxicity of cytokines in lung cells in vitro. These data support the proposal that inosine might represent a useful adjunct in the therapy of acute respiratory distress syndrome.