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H Ao

Publications and source records attributed to H Ao.

12 recordsLinked to original sources
PubMed2006

Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat.

Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia.

Acute Disease↗
PubMed2001

Long-term mild hypothermia with extracorporeal lung and heart assist improves survival from prolonged cardiac arrest in dogs.

BACKGROUND AND PURPOSE: although normothermic extracorporeal lung and heart assist (ECLHA) improves cardiac outcomes, patients can not benefit from hypothermia-mediated brain protection. The present study evaluated the effects of long-term ECLHA with mild to moderate hypothermia (33 degrees C) in a canine model of prolonged cardiac arrest. METHODS: 15 dogs were assigned to either the hypothermic (seven dogs, 33 degrees C) or normothermic group (eight dogs, 37.5 degrees C). All dogs were induced to normothermic ventricular fibrillation (VF) for 15 min, followed by 24 h of ECLHA and 72 h of intensive care. The hypothermia group maintained core (pulmonary artery) temperature at 33 degrees C for 20 h starting from resuscitation, then were rewarmed by 28 h. Outcome evaluations included: (1) mortality; (2) catecholamine dose; (3) time to extubation; (4) necrotic myocardial mass (g); and (5) neurological deficits score (NDS). RESULTS: in the normothermic group five dogs died of cardiogenic shock and one dog succumbed to poor oxygenation. The two surviving dogs remained comatose (NDS 60.5 +/- 4.9%) with necrotic myocardial mass of 14.5 +/- 3.5 g. In the hypothermic group, one dog died from pulmonary dysfunction, the other six dogs survived. The surviving dogs showed brain damage (29.8 +/- 2.5%), but there was evidence of some brain-protective effect. The mass of necrotic myocardium was 4.2 +/- 1.3 g in the hypothermic group or 3.4 times smaller than in the normothermic group. The survival rate was significantly higher in the hypothermic than in the normothermic group (P < 0.05). The catecholamine requirement was also lower in the hypothermic than in the normothermic dogs (P < 0.05). CONCLUSIONS: Long-term mild to moderate hypothermia with ECLHA induced immediately after cardiac arrest improved survival as well as cerebral and cardiac outcomes.

Analysis of Variance↗
PubMed2001

Delayed platelet dysfunction in prolonged induced canine hypothermia.

UNLABELLED: Mild to moderate hypothermia (33-32 degrees C) is recognized as beneficial for brain protection after brain trauma. However, there are few experimental reports on hemostatic changes during prolonged hypothermia. We compared hemostatic changes during 72 h of mild to moderate hypothermia with data in normothermic dogs. METHOD: Mongolian dogs in a hypothermic group (N=7, 33 degrees C core temperature) and normothermic group (N=6, 37.5 degrees C core temperature) were anesthetized and instrumented to control temperatures and record hemodynamic changes continuously. Hypothermia or normothermia was maintained for 72 h. Platelet count, platelet aggregation, and thromboelastograms (TEG) were measured in each group. RESULTS: Heart rate, blood pressure, pulmonary pressure and blood gas were not significantly different between the two groups. Platelet counts, compared to baseline values, were significantly decreased in both groups (P<0.01). Platelet aggregation was significantly decreased in the hypothermic group after 24 h (P<0.04). CONCLUSION: Long-term hypothermia induced platelet dysfunction, leading to decreased platelet aggregation and prolonged coagulation time (R and K times of TEG).

Animals↗
PubMed2001

Experimental evaluation of the V-point heparin-bonding system applied to a dense-membrane artificial lung during 24-hour extracorporeal circulation in beagles.

Heparin was covalently bonded to a hollow-fiber dense-membrane artificial lung and circuit using a silane coupling agent and polyethyleneimine as a spacer. This study investigated whether the novel artificial lung could sustain prolonged extracorporeal lung assist (ECLA) by venoarterial bypass in beagles using minimal anticoagulants. We maintained ECLA for 24 h in 3 groups of minimal systemic heparinization, heparinization with the new anticoagulant nafamostat mesilate, and without any systemic anticoagulant. The results were assessed from the functional performance of the artificial lung and by macroscopic and microscopic examination after the experiments. Artificial lung function, hemodynamics, hemogram, and platelet aggregation activity were well maintained in all groups. There was no plasma leakage from the artificial lung. Although several clots were observed in stagnant areas of the artificial lungs and circuits, there was no clot formation inside the artificial lung in any group. This highly biocompatible, heparin-bonded dense-membrane artificial lung performed well and safely during prolonged ECLA with blood clotting times less than 120 s.

Animals↗
PubMed2001

[Production of transgenic lamb integrated with modified human anti-trypsin gene].

This experiment is to produce the human mAAT(modified anti-trypsin) which cures the emphysema specifically through mammalian galactophore of transgenic goat. 56 goats were selected as donor for superovulation by FSF + LH microinjection in this experiment. The pronucleic embryos were injected with human mAAT gene after fertilization in vivo, and transferred to the donors or receptors directly. The superovulation was better in March and May than in December with the number of ovulation of 19.50, 21.70 and 16.06, and number of fertilized embryos of 4.31, 6.48 and 3.57 per-animal respectively. The pregnant rates were 18.18% and 25% respectively after transferred to donors and receptors with natural estrus. The donors also can be used as the embryo receptor with no remarkable decrease of pregnant rate. 29 lamb were labored. 4 positive transgenic lamb were checked by PCR, PCR-Southern and Southern analysis. The integrated efficiency of foreign DNA was 13.79% with microinjection of high copy number of foreign DNA fragment.

Animals↗
PubMed2000

Jugular vein temperature reflects brain temperature during hypothermia.

PURPOSE: The neuroprotective properties of mild to moderate hypothermia are well recognized but may not be employed correctly because brain temperature cannot usually be measured directly. This study investigated the jugular vein as a more accessible site that accurately reflects the actual brain temperature during mild, induced hypothermia. METHODS: We selected ten mongrel dogs (mean weight 12 +/- 2 kg) and measured temperatures of the brain, jugular vein, cisterna magna, pulmonary artery and rectum during hypothermia, including cooling and rewarming. The brain temperature needle probe was inserted 2.0 cm into the parenchyma. A temperature probe was placed in the cisterna magna with an epidural needle. Swan-Ganz thermistor probes measured the jugular venous and pulmonary artery blood temperatures. RESULT: The brain temperature decreased from 37.5 +/- 0.3 to 33.0 +/- 0.3 degrees C over an average 150 +/- 45 min cooling period. Stable cool was maintained for 245 +/- 32 min, followed by 165 +/- 50 min for rewarming from 33.5 +/- 0.3 to 37.5 +/- 0.3 degrees C. Jugular, cisterna magna and pulmonary arterial blood (PAB), but not rectal temperature, were close to brain temperature during stable cool. The mean jugular and cisterna magna temperatures were near the brain temperature at 0.1 degrees C higher and 0.1 degrees C lower, respectively. No significant effects of hypothermia were noted on hemodynamics in any phase. CONCLUSION: Jugular vein temperature, along with cisterna magna and pulmonary artery blood and rectal temperature, reflected brain temperature during hypothermia. The jugular vein and cisterna magna sites more sensitively reflected brain temperature than other sites.

Animals↗
PubMed2000

Total and prolonged filling of the lungs with Ringer's solution under extracorporeal lung assist (ECLA) in dogs.

BACKGROUND: Massive alveolar lavage has been used clinically to remove materials accumulated in the alveoli. Recently, filling the lungs with oxygenated perfluorochemical (total liquid ventilation) has been investigated. However, effects of complete and prolonged filling of bilateral lungs with aqueous fluid, such as saline or Ringer's solution, has not been evaluated, although it is possible to sustain gas exchange without the natural lung by using extracorporeal circulation and an artificial lung (extracorporeal lung assist: ECLA). It is also not known whether the lung can recover gas exchange ability after prolonged fluid filling. METHODS: Normal mongrel dogs were endotracheally intubated under general anesthesia and mechanically ventilated. After initiation of venoarterial ECLA, warmed lactated Ringer's solution was instilled into the lungs through the endotracheal tube, and the lungs were completely filled at a hydrostatic pressure of 15 cmH2O (fluid-filled group: group F). After the lungs were filled for 4 h, the fluid was drained and ventilation was re-instituted. ECLA, then mechanical ventilation was gradually weaned within 24 h after fluid drainage. In control group (group C), dogs were kept apneic for 4 h with their lungs inflated at an airway pressure of 15 cmH2O with air. RESULTS: Transient hypoxemia occurred during fluid filling but every dog could be weaned from ECLA and mechanical ventilation to spontaneous respiration. The average rate of fluid absorption from the lung during fluid filling was 4.2+/-1.8 ml kg(-1) h(-1). After fluid drainage and restart of mechanical ventilation, bilateral lungs were expanded and well aerated. Total static respiratory system compliance (static compliance) remained unchanged even after fluid filling, and the weight of the lung water did not increase significantly compared to that in group C. Total urine volume was significantly increased in group E Histologically, alveolar structures were preserved and no interstitial edema or bleeding was seen in either group. CONCLUSION: Complete filling of the bilateral lungs for 4 h with lactated Ringer's solution under ECLA causes no deterioration in gas exchange or static compliance in normal dogs, although transient hypoxemia occurs during fluid filling.

Animals↗
PubMed2000

Sero- and molecular typing of Duffy blood group in Southeast Asians and Oceanians.

Duffy blood group was studied among malaria-endemic Thai and Indonesian populations: Hmong (n = 103), Akha (n = 218), Lisu (n = 44), Bugis (n = 95), Toraja (n = 77), Dani (n = 44), Mee (n = 80) and Irianese (n = 81). Phenotypes were studied by the ordinal indirect Coombs' test and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test. DNA analysis was used to type the Duffy blood group system. Deduced allele frequencies of Fya (0.958-1.0) based on the phenotypes were similar to those in other populations in Southeast Asia and Oceania. The study revealed the presence of Fya-antigens showing weak reactivity to antisera as well as a discrepancy between the genotype shown by the PCR-RFLP study and that predicted by the phenotype. The PCR-RFLP study also suggested the presence of an alternative genetic basis for the Fy(a- b-) phenotype, which differs from the African type.

Alleles↗
PubMed1999

Molecular cloning of the Lon protease gene from Thermus thermophilus HB8 and characterization of its gene product.

The gene encoding Lon protease was isolated from an extreme thermophile, Thermus thermophilus HB8. Sequence analysis demonstrated that the T. thermophilus Lon protease gene (TT-lon) contains a protein-coding sequence consisting of 2385 bp which is approximately 56% homologous to the Escherichia coli counterpart. As expected, the G/C content of TT-lon was 68%, which is significantly higher than that of the E. coli lon gene (52% G/C). The amino acid sequence of T. thermophilus Lon protease (TT-Lon) predicted from the nucleotide sequence contained several unique sequences conserved in other Lon proteases: (a) a cysteine residue at the position just before the putative ATP-binding domain; (b) motif A and B sequences required for composition of the ATP-binding domain; and (c) a serine residue at the proteolytic active site. Expression of TT-lon under the control of the T7 promoter in E. coli produced an 89-kDa protein with a yield of approximately 5 mg.L-1. Recombinant TT-Lon (rTT-Lon) was purified to homogeneity by sequential column chromatography. The peptidase activity of rTT-Lon was activated by ATP and alpha-casein. rTT-Lon cleaved succinyl-phenylalanyl-leucyl-phenylalanyl-methoxynaphthylamide much more efficiently than succinyl-alanyl-alanyl-phenylalanyl-methoxynaphthylamide, whereas both peptides were cleaved with comparable efficiencies by E. coli Lon. These results suggest that there is a difference between TT-Lon and E. coli Lon in substrate specificity. rTT-Lon most effectively cleaved substrate peptides at 70 degrees C, which was significantly higher than the optimal temperature (37 degrees C) for E. coli Lon. Together, these results indicate that the TT-lon gene isolated from T. thermophilus HB8 actually encodes an ATP-dependent thermostable protease Lon.

ATP-Dependent Proteases↗
PubMedDate not supplied

Heparin bonding of the extracorporeal circuit reduces thrombosis during prolonged lung assist in goats.

This study investigated whether an artificial membrane lung of nonmicroporous polyolefin hollow fibers bonded with heparin could prolong venoarterial extracorporeal lung assist (ECLA) with low dose systemic heparin in goats. We compared heparin bonded circuits (Carmeda Bioactive Surface, "HB" group, n = 5) with non heparin bonded circuits ("NHB" group, n = 5) in venoarterial ECLA (V-A ECLA) for 7 days. Activated coagulation time (ACT) was maintained at approximately 130 sec by systemic infusion of small doses of heparin in the HB group, and at 200-230 sec in the NHB group. Thrombus formation was assessed by visual examination of the circuit, and possible cerebral embolization of thrombi was observed from behavioral abnormalities of the animals. The mean heparin dose given during ECLA was 20.4 +/- 3.6 U/kg per hr in HB, and 50.9 +/- 14.2 U/kg per hr in NHB, significantly less in HB than NHB (p < 0.01). Blood gas changes across the oxygenator, bypass flow rate, platelet aggregation activity, platelet counts, fibrin monomer (FM) test, and antithrombin-III (AT-III) activity did not differ between the two groups. In HB, thrombi were fewer and no abnormal neurologic symptoms were observed during ECLA. Numerous thrombi were observed in all oxygenators with NHB. One NHB goat developed convulsions and cerebral hemorrhage on the 6th day of ECLA. Nonmicroporous polyolefin hollow fibers can be bonded with heparin. An artificial membrane lung constructed of these fibers showed good anticoagulation by decreased thrombus formation with a small dose of infused heparin.

Animals↗