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Biomedical subjects

Ning Zhang

Publications and source records attributed to Ning Zhang.

At least 127 records · Page 7Linked to original sources

[Mossy fiber sprouting and synapse formation in the dentate gyrus of temporal lobe epilepsy rats induced by pilocarpine].

OBJECTIVE: To investigate the relationship between mossy fiber axon sprouting (MFS), synaptic reorganization in the dentate gyrus, and the mechanism of chronic temporal lobe epilepsy induced by pilocarpine. METHODS: The mossy fiber sprouting and synapse formation were observed in rats after the acute status epileticus and chronic spontaneous temporal lobe epilepsy induced by pilocarpine using in situ hybridization of GAP-43 mRNA (a marker of MFS), an immunohistochemical staining of synaptophysin (P38, a marker of synaptogenes), and Neo-Timm staining. RESULTS: In hippocampus granule cell, there was a significant increase in the GAP-43mRNA levels measured 6 - 12 h after the end of status epileticus induced by pilocarpine. In contrast, synaptophysin immunoreactivity progressively increased in the molecular layer of the dentate gyrus from 7 d, which was in line with the Neo-Timm stain results that revealed a time-dependent growth of aberrant MFS into the dentate inner molecular layer. The GAP-43 mRNA levels in pilocarpine treated animals were significantly decreased after status epileticus. CONCLUSION: These results provide evidence for newly formed excitatory recurrent circuits, which might constitute a structural basis for chronic enhanced excitation and epileptogenesis in the hippocampus of pilocarpine-treated rats.

Animals↗

[Changes and clinical significance of serum IL-6, sICAM-1 in patients with cerebral infarcts].

OBJECTIVE: To analyze the changes and clinical significance of IL-6 and sICAM-1, and to explore their pathologic mechanism in the brain ischemia. METHODS: Thirty-two patients at Xiangya Hospital who experienced infarcts that occurred within the first 3 days were consecutively selected into the study, and 30 healthy subjects were selected as controls. The serum level of IL-6 and sICAM-1 was measured by radioimmunoassy and enzyme linked immunosorbent assay. Eleven out of the 32 patients that experienced stroke within 24 hours were observed on the 1st, 3rd, and 6th day. The subsequent volume of brain lesion as a consequence of stroke was measured by CT within 48 - 72 hours after the onset. RESULTS: Both the serum levels of IL-6 and sICAM-1 were significantly higher in patients within the first 3 days after the onset than those of the controls [(352. 1 +/- 31.7) pg/ml vs. (135.4 +/- 18.3) pg/ml, and (363.6 +/- 48.4) ng/ml vs. (227.2 +/- 30.1) ng/ml, P < 0.01]. The levels of IL-6 at the 6th day [(308.3 +/- 26.8) pg/ml] was significantly lower than that both on the 1st day [(364.5 +/- 29.7) pg/ml] and on the 3rd day [(345 +/- 28.9) pg/ml] (P <0.01). There was no significant difference between the 1st day and the 3rd day (P > 0.05). Statistical significance existed in each two concentrations of sICAM-1 on the 1st day [(383.9 +/- 56.1) ng/ml], the 3rd day [(354.6 +/- 40.8) ng/ml], and the 6th day [(316.7 +/- 32.3) ng/ml] (P < 0.05). Both the levels of IL-6 and sICAM-1 were higher in patients within the 6th day after the onset than those of sICAM-1 on the controls (P < 0.01). There was a positive correlation between both the levels of IL-6 and sICAM-1 at the first 3 days after the onset and the infarct volume (r = 0. 368, P < 0. 05 and r = 0. 594, P < 0. 01) , and the sICAM-1 positively correlated with IL-6 (r = 0. 453, P < 0. 05). CONCLUSION: The serum levels of IL-6 and sICAM-1 were upregulated, which might play a role in inflammatory lesion, and the upregulation of sICAM-1 may be related to the IL-6. The levels of IL-6 and sICAM-1 may reflect both the degree of pathologic lesion after the brain ischemia and the infarct volume.

Biomarkers↗

Potent inhibition of NTPase/helicase of the West Nile Virus by ring-expanded ("fat") nucleoside analogues.

A series of ring-expanded ("fat") nucleoside analogues (RENs) containing the 6-aminoimidazo[4,5-e][1,3]diazepine-4,8-dione ring system have been synthesized and screened for inhibition of NTPase/helicase of the West Nile Virus (WNV). To assess the selectivity of RENs against the viral enzymes, a truncated form of human enzyme Suv3((Delta)(1)(-)(159)) was also included in the study. Ring-expanded nucleosides 16, 17, and 19, which possess the long C(12), C(14), and C(18) side-chains, respectively, at position 6, as well as the ring-expanded heterocycle 39, which contains aralkyl substitution at position 1, were all found to have excellent profiles of activity and selectivity toward the viral versus human enzymes against the West Nile Virus (IC(50) ranging 1-10 muM). Compound 30, while being an equally potent inhibitor of WNV, was found to be somewhat less selective, whereas compound 36, which is an alpha-anomeric counterpart of 30, exhibited potent and selective inhibition of WNV (IC(50) 1-3 muM). The same compounds that showed potent inhibition of viral helicase activity completely failed to show any activity against the viral NTPase reaction even up to 500 muM. However, at concentrations >500 muM of RENs and the ATP concentrations >10 times the K(m) value of the enzyme, a significant activation of NTPase activity was observed. This activating effect underwent further dramatic enhancement (>1000%) by further increases in ATP concentration in the reaction mixture, suggesting that the viral helicase and NTPase reactions are not coupled. A tentative mechanistic model has been proposed to explain the observed results.

Acid Anhydride Hydrolases↗

Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse.

The vascular endothelial growth factor-2 (VEGFR2) gene is transcriptionally regulated during angiogenesis. The ability to monitor and quantify VEGFR2 expression in vivo may facilitate a better understanding of the role of VEGFR2 in different states. Here we describe a transgenic mouse, Vegfr2-luc, in which a luciferase reporter is under control of the murine VEGFR2 promoter. In adult mice, luciferase activity was highest in lung and uterus, intermediate in heart, skin, and kidney, and lower in other tissues. Luciferase expression in these tissues correlated with endogenous VEGFR2 mRNA expression. In a cutaneous wound-healing model, Vegfr2-luc expression was induced in the wound tissue. Histologic and immunohistochemical studies showed significant macrophage infiltration into the wound and induction of Vegfr2-luc expression in endothelial and stromal cells. Dexamethasone significantly suppressed Vegfr2-luc expression and macrophage infiltration into the wound, resulting in delayed healing and impaired angiogenesis. In a skin hypersensitivity reaction produced by treatment with oxazolone, Vegfr2-luc expression was induced in the ear. Treatment by dexamethasone markedly suppressed Vegfr2-luc expression and leukocyte infiltration in the ear and was correlated with reduced dermal edema and epidermal hyperplasia. The Vegfr2-luc model will be valuable in monitoring the ability of drugs to affect angiogenesis in vivo.

Animals↗

Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization.

The opiates are well-established immunomodulatory factors, and recent evidence suggests that mu- and delta-opioid receptor ligands alter chemokine-driven chemotactic responses through the process of heterologous desensitization. In the present report, we sought to examine the capacity of mu- and delta-opioids to modulate the function of chemokine receptors CCR5 and CXCR4, the two major human immunodeficiency virus (HIV) coreceptors. We found that the chemotactic responses to the CCR1/5 ligand CCL5/regulated on activation, normal T expressed and secreted, but not the CXCR4 ligand stromal cell-derived factor-1alpha/CXCL12 were inhibited following opioid pretreatment. Studies were performed with primary monocytes and Chinese hamster ovary cells transfected with CCR5 and the micro-opioid receptor to determine whether cross-desensitization of CCR5 was a result of receptor internalization. Using radiolabeled-binding analysis, flow cytometry, and confocal microscopy, we found that the heterologous desensitization of CCR5 was not associated with a significant degree of receptor internalization. Despite this, we found that the cross-desensitization of CCR5 by opioids was associated with a decrease in susceptibility to R5 but not X4 strains of HIV-1. Our findings are consistent with the notion that impairment of the normal signaling activity of CCR5 inhibits HIV-1 coreceptor function. These results have significant implications for our understanding of the effect of opioids on the regulation of leukocyte trafficking in inflammatory disease states and the process of coreceptor-dependent HIV-1 infection. The interference with HIV-1 uptake by heterologous desensitization of CCR5 suggests that HIV-1 interaction with this receptor is not passive but involves a signal transduction process.

Acquired Immunodeficiency Syndrome↗

Ring-expanded ("fat") nucleoside and nucleotide analogues exhibit potent in vitro activity against flaviviridae NTPases/helicases, including those of the West Nile virus, hepatitis C virus, and Japanese encephalitis virus.

A series of ring-expanded ("fat") heterocycles, nucleoside and nucleotide analogues (RENs) containing the imidazo[4,5-e][1,3]diazepine ring system (9, 14, 15, 18, 24-26, 28, 31, and 33) and imidazo[4,5-e][1,2,4]triazepine ring systems (30b, 30c, 32, and 34), have been synthesized as potential inhibitors of NTPases/helicases of Flaviviridae, including the West Nile virus (WNV), hepatitis C virus (HCV), and Japanese encephalitis virus (JEV). An amino-terminal truncated form of human enzyme Suv3(delta1-159) was also included in the study so as to assess the selectivity of RENs against the viral enzymes. The analogues of RENs included structural variations at position 1 of the heterocyclic base and contained changes in both the type of sugar moieties (ribo, 2'-deoxyribo, and acyclic sugars) and the mode of attachment (alpha versus beta anomeric configuration) of those sugars to the heterocyclic base. The target RENs were biochemically screened separately against the helicase and ATPase activities of the viral NTPases/helicases. A number of RENs inhibited the viral helicase activity with IC50 values that ranged in micromolar concentrations and exhibited differential selectivity between the viral enzymes. In view of the observed tight complex between some nucleosides and RNA and/or DNA substrates of a helicase, the mechanism of action of RENs might involve their interaction with the appropriate substrate through binding to the major or minor groove of the double helix. The REN-5'-triphosphates, on the other hand, did not influence the above unwinding reaction, but instead exerted the inhibitory effect on the ATPase activity of the enzymes. The activity was found to be highly dependent upon the low concentration levels of the substrate ATP. At concentrations >500 microM of RENs and the ATP concentrations >10 times the Km value of the enzyme, a significant activation of NTPase activity was observed. This activating effect underwent further dramatic enhancement (>1000%) by further increases in ATP concentration in the reaction mixture. A tentative mechanistic model has been proposed to explain the observed results, which includes an additional allosteric binding site on the viral NTPases/helicases that can be occupied by nucleoside/nucleotide-type molecules such as RENs.

Adenosine Triphosphatases↗

Molecular profile of the unique species of traditional Chinese medicine, Chinese seahorse (Hippocampus kuda Bleeker).

A cDNA library of male Chinese seahorse (Hippocampus kuda Bleeker) was constructed to investigate the molecular profile of seahorse as one of the most famous traditional Chinese medicine materials, and to reveal immunological and physiological mechanisms of seahorse as one of the most primitive vertebrates at molecular level. A total of 3372 expressed sequence tags (ESTs) consisting of 1911 unique genes (345 clusters and 1566 singletons) were examined in the present study. Identification of the genes related to immune system, paternal brooding and physiological regulation provides not only valuable insights into the molecular mechanism of immune system in teleost fish but also plausible explanations for pharmacological activities of Chinese seahorse. Furthermore, the occurrence of high prevalent C-type lectins suggested that a lectin-complement pathway might exert a more dominant function in the innate immune system of teleost than mammal. Carbohydrate recognition domain (CRD) without a collagen-like region in the lectins of seahorse was likely an ancient characteristic of lectins similar to invertebrates.

Amino Acid Sequence↗

An inducible nitric oxide synthase-luciferase reporter system for in vivo testing of anti-inflammatory compounds in transgenic mice.

The inducible NO synthase gene (iNOS) plays a role in a number of chronic and acute conditions, including septic shock and contact hypersensitivity autoimmune diseases, such as rheumatoid arthritis, gastrointestinal disorders, and myocardial ischemia. The iNOS gene is primarily under transcriptional control and is induced in a variety of conditions. The ability to monitor and quantify iNOS expression in vivo may facilitate a better understanding of the role of iNOS in different diseases. In this study, we describe a transgenic mouse (iNos-luc) in which the luciferase reporter is under control of the murine iNOS promoter. In an acute sepsis model produced by injection of IFN-gamma and LPS, we observed an induction of iNOS-driven luciferase activity in the mouse liver. This transgene induction is dose and time dependent and correlated with an increase of liver iNOS protein and iNOS mRNA levels. With this model, we tested 11 compounds previously shown to inhibit iNOS induction in vitro or in vivo. Administration of dexamethasone, epigallocatechin gallate, alpha-phenyl-N-tert-butyl nitrone, and ebselen significantly suppressed iNOS transgene induction by IFN-gamma and LPS. We further evaluated the use of the iNos-luc transgenic mice in a zymosan-induced arthritis model. Intra-articular injection of zymosan induced iNos-luc expression in the knee joint. The establishment of the iNos-luc transgenic model provides a valuable tool for studying processes in which the iNOS gene is induced and for screening anti-inflammatory compounds in vivo.

Acute Disease↗

Luminescence behavior of a water soluble calix[4]arene derivative complex with terbium ion(III) in gelation solution.

The complexation luminescence behavior of a water soluble calix[4]arene derivative, 5,11,17,23-tetra-sulfonate-25,26,27,28-tetra-carboxymethoxycalix[4]arene (L) with lanthanoid ion (Tb(3+)) has been investigated in gelation solution at 25 degrees C by using UV-vis and fluorescence spectra. The results obtained indicated that the water soluble calix[4]arene derivative can form an efficient energy transfer complex with terbium ion(III). The fluorescence of L x Tb(3+)complex is partially quenched by gelatin in gelation solution. The quenching intensity is related to the concentration and the hydrolysis degree of gelatin. Absorption and fluorescence spectra analysis show that the -COO(-) groups on gelatin have a definite binding ability to Tb(3+), and then, gelatin could compete binding with calix[4]arene derivative upon complexation with Tb(3+), leading to the relative fluorescence quenching of the formation complex of terbium(III) ion with calix[4]arene derivative.

Calixarenes↗

[Expression of MMP-2, MMP-9 and TIMP-1 and the effects of methylprednisolone in EAM].

OBJECTIVE: To study the function of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9) and TIMP-1 (tissue inhibitor of metalloproteinase-1) in the pathogenesis of EAM (experimented autoimmune myositis) rats, and to evaluate the effect of methylprednisolone on the mRNA and protein expression of MMP-2, MMP-9 and TIMP-1. METHODS: The expression levels of MMP-2, MMP-9 and TIMP-1 in the peripheral blood, spleen lymphocytes and muscles were examined among the EAM group, EAMM group and control group by RT-PCR and immunohistochemical techniques. RESULTS: 1. The degree of episode in the EAMM group was lower than that in the EAM group. Also, the infiltration of the inflammatory cells and the necrosis of the muscles were milder in the EAMM group than those in the EAM group. 2. The mRNA expression of MMP-2 and MMP-9 in the lymphocytes of the peripheral blood and spleen and the protein expression of MMP-2 and MMP-9 in the muscle tissues all increased significantly in the EAM group compared with those of the control group. However, the mRNA and protein expression of MMP-2 and MM-9 was suppressed significantly in contrast with that in the EAM group. 3. The mRNA and protein expression of TIMP-1 in the EAMM group increased with statistical significance compared with that in the EAM group. CONCLUSION: The upregulation of the expression of MMP-2 and MMP-9 may be related with the onset of EAM. TIMP-1 may be involved in the suppression of immunoreaction. Methylprednisolone may reduce the pathological damages of EAM, and this protective mechanism may be due to the inhibited expression of MMP-2 and MMP-9 and promoted expression of TIMP-1.

Animals↗

Ca2+-independent protein kinase Cs mediate heterologous desensitization of leukocyte chemokine receptors by opioid receptors.

Heterologous desensitization of chemokine receptors by opioids has been considered to contribute to their immunosuppressive effects. Previous studies show that Met-enkephalin, an endogenous opioid, down-regulates chemotaxis of selected chemokine receptors via phosphorylation. In the present study, we further investigated the molecular mechanism of such cross-regulation. Our data showed that preincubation with Met-enkephalin inhibited both MIP-1 alpha-mediated chemotaxis and Ca(2+) flux of monocytes in a dose-dependent manner. The inhibitory effects were maximal using nanomolar concentrations of activating chemokines, a concentration found in physiological conditions. A decrease both in chemokine receptor affinity and in coupling efficiency between receptors and G protein were observed, which directly contributed to the desensitization effects. However, comparing with chemokines such as MIP-1 alpha and MCP-1, opioids did not elicit a calcium flux, failed to induce MIP-1 alpha receptors internalization, and mediated a less potent heterologous desensitization. We hypothesized that these differences might originate from the involvement of different protein kinase C (PKC) isotypes. In our studies, opioid-mediated down-regulation of MIP-1 alpha receptors could be blocked by the general PKC inhibitor calphostin C, but not by the calcium-dependent classic PKC inhibitor Go6976. Western blotting analysis and immunofluorescent staining further showed that only calcium-independent PKCs were activated upon opioid stimulation. Thus, opioids achieve desensitization of chemokine receptors via a unique pathway, involving only calcium-independent PKC isotypes.

Calcium↗

A nonradioactive method for detecting DNA-binding activity of nuclear transcription factors.

To determine the feasibility of a nonradioactive electrophoresis mobility shift assay for detecting nuclear transcription factor, double-stranded oligonucleotides encoding the consensus target sequence of NF-kappa B were labelled with DIG by terminal transferase. After nuclear protein stimulated with phorbol 12-myristate 13-acetate (PMA) or PMA and pyrrolidine dithiocarbamate (PDTC) electrophoresed on 8% nondenaturing poliacrylamide gel together with oligeonucleotide probe, they were electro-blotted nylon membrane positively charged. Anti-DIG-AP antibody catalyzed chemiluminescent substrate CSPD to image on X-film. The results showed that nuclear proteins binded specifically to the NF-kappa B consensus sequence in the EMSA by chemiluminescent technique method and the activity of NF-kappa B in PMA group was more than that in PMA + PDTC group. It is suggested that detection of NF-kappa B by EMSA with chemiluminescent technique is feasible and simple, which can be performed in ordinary laboratories.

Animals↗

Cerebral physiology and outcome after hypothermic circulatory arrest followed by selective cerebral perfusion.

BACKGROUND: This study explored the impact of an interval of hypothermic circulatory arrest (HCA) preceding selective cerebral perfusion (SCP) on cerebral physiology and outcome. This protocol allows use of SCP during aortic surgery without the threat of embolization inherent in balloon catheterization of often severely atherosclerotic cerebral vessels. METHODS: In this blinded study, 30 pigs (20 to 22 kg) were randomized after cooling to 20 degrees C. Pigs in the HCA-CPB group (n = 10) underwent 30 minutes of HCA followed by 60 minutes of total body perfusion (CPB); HCA-SCP pigs (n = 10) underwent 30 minutes of HCA followed by 60 minutes of SCP, and SCP pigs (n = 10) had 90 minutes of SCP without prior HCA. Fluorescent microspheres enabled calculation of cerebral blood flow during perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular resistance, and cerebral oxygen consumption were also monitored. Daily behavioral scores were obtained for 7 days postoperatively. RESULTS: In all groups, cerebral oxygen consumption fell significantly with cooling (p < 0.0001), remained low during perfusion, and rebounded promptly with rewarming; cerebral oxygen consumption was significantly (p = 0.027) greater during SCP than during HCA-CPB. Cerebral blood flow was significantly higher throughout SCP in the HCA-SCP group (p < 0.0001) than with CPB. Cerebrovascular resistance during SCP and HCA-SCP was significantly lower (p = 0.036) than during CPB. Behavioral scores were significantly better with SCP than with HCA-CPB throughout recovery, but did not differ between SCP and HCA-SCP. CONCLUSIONS: This study suggests that a short period of HCA preceding SCP provides global cerebral protection comparable to continuous SCP, implying that in clinical practice, a short period of HCA to reduce risk of embolization will not compromise the superior cerebral protection provided by SCP.

Animals↗

Microorganisms in the gut of beetles: evidence from molecular cloning.

We have regularly cultured yeasts from the gut of certain beetles in our ongoing research. In this study cloned PCR products amplified from the gut contents of certain mushroom-feeding and wood-ingesting beetles in four families (Erotylidae, Tenebrionidae, Ciidae, and Passalidae) were sequenced and compared with culture results. Cultural techniques detected some yeasts present in the gut of the beetles, including a Pichia stipitis-like yeast associated with wood-ingesting passalid beetles. Clone sequences similar to several ascomycete yeasts and Malassezia restricta, a fastidious basidiomycetous yeast requiring special growth media, however, were not detected by culturing. Unexpectedly, phylogenetic analysis of additional clone sequences discovered from passalid beetles showed similarity to members of the Parabasalia, protists known from other wood-ingesting insects, termites, and wood roaches. Examination of all gut regions of living passalids, however, failed to reveal parabasalids, and it is possible that they were parasites in the gut tissue present in low numbers.

Animals↗

Importance of extrasegmental vessels for spinal cord blood supply in a chronic porcine model.

OBJECTIVE: Our purpose was to investigate the interaction of the important components of spinal cord blood supply in the pig model to enable its use for future studies of spinal cord protection. METHODS: Twenty-five juvenile pigs (20-22 kg) underwent serial intercostal (IC) or lumbar artery (LA) ligation until disappearance of motor evoked potentials (MEPs). Pigs underwent sequential craniocaudal IC/LA ligation alone (n=5); following clamping of both subclavian arteries (n=4), or clamping of the median sacral artery (MSA, n=4). Animals also underwent serial caudocranial clamping of LA/IC alone (n=4); preceded by clamping of the subclavian arteries (n=4), or of the MSA (n=4). Results were verified by Tarlov's scores and perioperative angiography. RESULTS: All animals with MEP loss suffered postoperative paraplegia. Groups were equivalent with regard to stable arterial pressures (64.6+/-3.1 degrees C) throughout the experiment, temperature (36+/-1.1 degrees C) and other physiological parameters. Mean number of clamped IC/LA before MEP loss for cranio-caudal clamping direction was 12.8+/-0.8 for segmental arteries isolated, 9+/-0.8 if both subclavian arteries were ligated previously and only 4.3+/-0.5 IC if the median sacral artery was clamped before. Mean number of clamped LA for caudo-cranial clamping direction was 5.8+/-0.9 for segmental lumbar arteries, 5.5+/-0.6 LA if both subclavian arteries were ligated previously and 3.5+/-0.6 if the median sacral artery was clamped before. CONCLUSION: This study confirms the importance of lumbar and MSA arteries to cord viability. It documents the interaction of the subclavian and MSA (roughly equivalent to the hypogastric arteries in humans) with segmental vessels in providing spinal cord blood supply. It also provides the physiologic basis for use of the pig model for studies of spinal cord protection in aortic surgery.

Animals↗

Impact of hypothermic selective cerebral perfusion compared with hypothermic cardiopulmonary bypass on cerebral hemodynamics and metabolism.

OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic arch surgery, but the effect of the absence of systemic perfusion on cerebrovascular dynamics it has never been established. This study explored the physiology of prolonged SCP compared to hypothermic cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29 juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were injected during perfusion and recovery, enabling calculation of total and regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF decreased significantly (P=0.0001) during cooling, but remained at significantly higher levels with SCP than with HCPB throughout perfusion and recovery (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout perfusion (P=0.04). Oxygen consumption fell significantly with cooling (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming; with SCP it was significantly higher than with HCPB throughout the perfusion interval (P=0.03), and remained higher thereafter. ICP rose significantly less with SCP than with HCPB (P=0.02). CONCLUSION: We conclude that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by significantly higher CBF and oxygen consumption during SCP, by prompt recovery of oxygen consumption after rewarming, and by significantly lower ICP during perfusion and in the post-bypass period.

Animals↗

Defining forces that are associated with shoulder dystocia: the use of a mathematic dynamic computer model.

OBJECTIVE: A computer model was modified to study the impact of maternal endogenous and clinician-applied exogenous delivery loads on the contact force between the anterior fetal shoulder and the maternal symphysis pubis. STUDY DESIGN: Varying endogenous and exogenous loads were applied, and the contact force was determined. Experiments also examined the effect of pelvic orientation and the direction of load application on contact force behind the symphysis pubis. RESULTS: Exogenous loading forces (50-100 N) resulted in anterior shoulder contact forces of 107 to 127 N, with delivery accomplished at 100 N of applied load. Higher contact forces (147-272 N) were noted for endogenously applied loads (100-400 N), with delivery occurring at 400 N of maternal force. Pelvic rotation from lithotomy to McRoberts' positioning resulted in reduced contact forces. Downward lateral flexion of the fetal head led to little difference in contact force but required 30% more exogenous load to achieve delivery. CONCLUSION: Compared with clinician-applied exogenous force, larger maternally derived endogenous forces are needed to clear the impacted anterior fetal shoulder. This is associated with >2 times more contact force by the obstructing symphysis pubis. McRoberts' positioning reduces shoulder-symphysis pubis contact force. Lateral flexion of the fetal head results in the larger forces that are needed for delivery but has little effect on contact force. Model refinements are needed to examine delivery forces and brachial plexus stretching more specifically.

Delivery, Obstetric↗

Prediction of brachial plexus stretching during shoulder dystocia using a computer simulation model.

OBJECTIVE: The purpose was to study the impact of maternal endogenous and clinician-applied exogenous delivery forces on brachial plexus stretching during a shoulder dystocia event. STUDY DESIGN: A computer software crash dummy model (MADYMO, version 5.4, TNO Automotive, Delft, The Netherlands) was modified on the basis of established maternal pelvis and fetal anatomic specifications. The brachial plexus was modeled as a spring, with mechanical properties that were based on previously reported experimental data. Increasing amounts of endogenous or exogenous loading forces were applied until delivery of the anterior fetal shoulder occurred. Brachial plexus deformation was assessed as percent stretch in the nerve (Change in length/Original length x 100). RESULTS: With lithotomy positioning, both maternal endogenous and clinician-applied exogenous delivery forces were associated with brachial plexus stretching (15.7% vs 14.0%, respectively). McRoberts positioning reduced needed loading forces for delivery and resulted in 53% less brachial plexus stretch (6.6%). Downward lateral displacement of the fetal head was associated with a 30% increase in brachial plexus stretch (18.2%) compared with axial positioning of the head (14.0%). CONCLUSION: Brachial plexus stretch varied as a result of the load required for delivery, the source of the applied force, pelvic orientation, and fetal head positioning. Maternally derived and clinician-applied delivery forces can both lead to brachial plexus deformation when shoulder dystocia is encountered. The McRoberts maneuver can reduce brachial plexus stretching. Management of fetal head position may also be important in reducing unnecessary brachial plexus stretch.

Brachial Plexus↗