Variable decelerations are the most frequent fetal heart rate changes that are related to labor. The objective of the study
was to estimate the impact of non-significant variable decelerations (NSV) appearing during the latent phase of labor on delivery
mode and neonatal outcome. 相似文献
ObjectiveTo compare perinatal outcome and glycaemic control in two groups of pregnant diabetic patients receiving two insulin regimens.DesignRandomised controlled open label study.SettingUniversity affiliated hospital, Israel.Participants138 patients with gestational diabetes mellitus and 58 patients with pregestational diabetes mellitus received insulin four times daily, and 136 patients with gestational diabetes and 60 patients with pregestational diabetes received insulin twice daily.InterventionThree doses of regular insulin before meals and an intermediate insulin dose before bedtime (four times daily regimen), and a combination of regular and intermediate insulin in the morning and evening (twice daily regimen).ResultsMean daily insulin concentration before birth was higher in the women receiving insulin four times daily compared with twice daily: by 22 units (95% confidence interval 12 to 32) in patients with gestational diabetes and by 28 units (15 to 41) in patients with pregestational diabetes. Glycaemic control was better with the four times daily regimen than with the twice daily regimen: in patients with gestational diabetes mean blood glucose concentrations decreased by 0.19 mmol/l (0.13 to 0.25), HbA1c by 0.3% (0.2% to 0.4%), and fructosamine by 41 μmol/l (37 to 45), and adequate glycaemic control (mean blood glucose concentration <5.8 mmol/l) was achieved in 17% (8% to 26%) more women; in patients with pregestational diabetes mean blood glucose concentration decreased by 0.44 mmol/l (0.28 to 0.60), HbA1c by 0.5% (0.2% to 0.8%), and fructosamine by 51 μmol/l (45 to 57), and adequate glycaemic control was achieved in 31% (15% to 47%) more women. Maternal severe hypoglycaemic events, caesarean section, preterm birth, macrosomia, and low Apgar scores were similar in both dose groups. In women with gestational diabetes the four times daily regimen resulted in a lower rate of overall neonatal morbidity than the twice daily regimen (relative risk 0.59, 0.38 to 0.92), and the relative risk for hyperbilirubinaemia and hypoglycaemia was lower (0.51, 0.29 to 0.91 and 0.12, 0.02 to 0.97 respectively). The relative risk of hypoglycaemia in newborn infants to mothers with pregestational diabetes was 0.17 (0.04 to 0.74).ConclusionsGiving insulin four times rather than twice daily in pregnancy improved glycaemic control and perinatal outcome without further risking the mother.
Key messages
Improving maternal glycaemic control during pregnancy is the key to better perinatal outcome
In pregnant diabetic women insulin four times daily achieved better glycaemic control and lower rate of perinatal complications (hypoglycaemia, hyperbilirubinaemia) than insulin twice daily
Better glycaemic control resulted from a larger total daily insulin dose
The intensified regimen did not lead to higher rate of severe maternal hypoglycaemia
1. We studied responses of adult brine shrimp, Artemia franciscana, to high temperature, including LT50 determination, induced thermotolerance (ITT), the Hsp-70 family of stress proteins and protein synthesis before and after heat shock.
2. Adults were grown in laboratory cultures from encysted embryos (cysts) obtained from San Francisco Bay (SF) and much warmer culture ponds in Vietnam (V).
3. Adults from V cysts were more tolerant of high temperatures than those from SF cysts, but this difference essentially disappeared in the second generation of adults.
4. Levels of constitutive Hsc-70 were very low in adults of both groups, but were strongly upregulated by a sublethal heat shock (37°C, 30 min), with V adults showing the greater degree of upregulation. Heat shock also induced Hsp-67, to a greater extent in V compared to SF adults
5. Incorporation of 14C-leucine into protein did not result in the “classic” heat shock response, possibly due to increased permeability of heat-shocked animals to the tracer.
Immunotherapy with Bacillus Calmette–Guérin (BCG)—an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization—is a clinically established procedure for the treatment of superficial bladder cancer.
However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of
this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of
BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties,
and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free
equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating
the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy
must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can
lead to an over-stimulated immune system having dangerous side effects for the patient. 相似文献
Jasmonates are plant stress hormones that induce suppression of proliferation and death in cancer cells, while being selectively
inactive towards non-transformed cells. Jasmonates can overcome apoptotic blocks and exert cytotoxic effects on drug-resistant
cells expressing p53 mutations. Jasmonates induce a rapid depletion of ATP in cancer cells. Indeed, this steep drop occurs
when no signs of cell death are detectable yet. Experiments using modulators of ATP synthesis via glycolysis or oxidative
phosphorylation suggest that the latter is the pathway suppressed by jasmonates. Consequently, the direct effects of jasmonates
on mitochondria were evaluated. Jasmonates induced cytochrome c release and swelling in mitochondria isolated from cancer
cells but not from normal ones. Thus, the selectivity of jasmonates against cancer cells is rooted at the mitochondrial level,
and probably exploits differences between mitochondria from normal versus cancer cells. These findings position jasmonates
as promising anti-cancer drugs acting via energetic depletion in neoplastic cells. 相似文献
Release of apoptogenic proteins such as cytochrome c from mitochondria is regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic BH3-only proteins activating Bax and Bak. Current models assume that apoptosis induction occurs via the binding and inactivation of anti-apoptotic Bcl-2 proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze apoptosis induction by the BH3-only protein Bim(S). Regulated expression of Bim(S) in epithelial cells was followed by its rapid mitochondrial translocation and mitochondrial membrane insertion in the absence of detectable binding to anti-apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of Bax and apoptosis. Mutational analysis of Bim(S) showed that mitochondrial targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis induction. In yeast, Bim(S) enhanced the killing activity of Bax in the absence of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only protein can occur through a process that is independent of anti-apoptotic Bcl-2 proteins but requires mitochondrial targeting. 相似文献
We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity. 相似文献
Cancer is a result of complex changes that occur in normal cells as they transform to become malignant and further when they become metastatic. These changes are not a consequence of a single protein but rather involve multiple proteins that function in pathways and networks. Thus, profiling cancer-associated changes requires simultaneous measurement of many proteins in a single sample. Identifying these changes may lead to the discovery of cancer-associated biomarkers that may assist in diagnosis, prognosis, patient monitoring and possibly for therapeutic purposes. Antibody arrays are a relatively new technology that enables one to perform multiplex high-throughput protein expression profiling. This review describes current technologies in antibody array and assay design, and presents a survey of the current literature on the use of these arrays in cancer research. 相似文献