[Anesthetic Care of Children With Gene Therapy for the Treatment of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency].

AADC deficiency is a rare autosomal recessive disease that may lead to movement disorder and/or autonomic dysfunction. The prognosis of AADC deficiency patients is poor, and most die in childhood. Gene therapy is the only method currently available to help alleviate related symptoms. Gene therapy involves the injection of adeno-associated viral (AV) vector into the basal ganglia of patients, helping transfer the AADC gene and leading to improved AADC production and higher numbers of neurotransmitters in the brain. Moreover, as patients are unable to produce catecholamine, they may also suffer from a disorder affecting the regulatory control of the autonomic nervous system, resulting in hypoglycemia, which often causes imbalances in thermoregulation and hemodynamic and functional adjustments during surgery. Furthermore, the use of analgesics and inhalational anesthetics increase the risks of hypotension and bradycardia. Thus, in addition to assessing cardiac and respiratory system functions, it is important to evaluate the patient's airway before administering anesthesia, as structural anomalies or other situations may be present that lead to difficulties in tracheal intubation. Various airway tools, anesthesia equipment, and alternative plans should thus be prepared to protect the airway and maintain vital signs. All of the abovementioned issues increase the risks of AADC deficiency patients undergoing general anesthesia. The development of gene transfection for genetic diseases is a future trend. This paper identifies possible problems and related responses in perioperative patient care during gene therapy. The authors hope that these experiences provide references for the administration of AADC and similar gene therapies in the future.

[Effects of jingjin acupuncture on fine activity of hemiplegic hand in recovery period of stroke].

OBJECTIVE: To observe improved effects of Jingjin acupuncture on fine activity of hemiplegic hand in recovery period of stroke. METHODS: Fifty cases were randomly divided into an observation group and a control group, 25 cases in each one. Regular western medicine treatment, rehabilitation training and regular acupuncture (in which Shuigou (GV 26), Baihui (GV 20), Neiguan (PC 6), etc. were selected) were applied in both groups. Additionally, muscles in palm side of affected hand, dorsal metacarpophalangeal joints and proximal interphalangeal joints were treated with acupuncture in the observation group, once every other day and electroacupuncture was applied when arrival of qi was acquired. Baxie (EX-UE 9) in the affected hand were needled in the control group, and electroacupuncture was added when arrival of qi was acquired. Ten days of treatment was considered a treatment course, and after two courses Lindmark score, Brunnstrom movement function grade, joint range of hand and Barthel index (BI) were observed in two groups. RESULTS: Compared before the treatment, the Lindmark score in two groups were both improved after the treatment (both P < 0.01). Compared with the control group, the motor coordination ability, sensory function and total score of Lindmark in observation group were obviously improved (differences before and after treatment: 8.24 +/- 3.07 vs 6.84 +/- 2.43, 3.52 +/- 2.33 vs 2.16 +/- 2.12, 11.76 +/- 3.55 vs 9.00 +/- 3.62, all P < 0.05). The Brunnstrom movement function grade was significantly improved in both groups after treatment (both P < 0.01), which was more obvious in the observation group (P < 0.05). The joint range of hemiplegic hand was improved in both groups after treatment (both P < 0.01), which was more obvious in the observation group [differences before and after treatment: (25.35 +/- 10.91) degrees vs (18.65 +/- 7.86) degrees, p < 0.05]. The score of BI was also significantly improved after treatment in two groups (both P < 0.01). CONCLUSION: The Jingjin acupuncture could effectively improve fine activity of hemiplegic hand in recovery period of stroke prove daily life ability.

Effects of dihydrotestosterone on adhesion and proliferation via PI3-K/Akt signaling in endothelial progenitor cells.

The protective effects of male hormones on the cardiovascular system are still in dispute. There is now ample evidence that testosterone level is negatively correlated to the incidence and mortality of cardiovascular disease in men. Endothelial progenitor cells (EPCs) play a vital role in endothelial healing and vascular integrity, which are useful for promoting cardiovascular health. In this study, we investigated the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on human EPC function and the activation of the phosphatidylinositol-3-kinase (PI3-K)/Akt pathway in vitro. EPCs were incubated with a series of concentrations (1, 10, or 100 nmol/L in DMSO) of DHT for 24 h or with 10 nmol/L DHT for different time (6, 12, 24, 48 h). EPC adhesion and proliferation and the activation of Akt were assayed by cell counting, 5-ethynyl-2'-deoxyuridine incorporation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis. Our data demonstrated that DHT significantly increased the proliferative activity and adhesive ability of EPCs in a dose- and time-dependent manner, maximum at 10 nmol/L, 24 h (p < 0.05). Western blot analysis revealed that DHT promoted the phosphorylation of Akt, and the effects of different concentrations of DHT on Akt phosphorylation were consistent with those on EPC proliferation and adhesion (p < 0.05). However, the enhancing effects of DHT on EPCs decreased with administration of the pharmacological PI3-K blocker LY294002 (p < 0.05). In conclusion, DHT can modulate EPC proliferation and adhesion and the PI3-K/Akt pathway plays an important role in this process.

Effect of sex on biomechanical properties of the proper hepatic artery in pigs and humans for liver xenotransplant.

OBJECTIVES: This study investigated the relation between biomechanical properties of the proper hepatic artery and sex in pigs and humans to provide the theoretical basis for selecting suitable donor in pig-to-human liver xenotransplant. MATERIALS AND METHODS: The proper hepatic arteries of 32 Chinese Hubei white pigs (8 males, 8 females, 8 castrated males, and 8 ovariectomized females) and 10 deceased donors (5 human men, 5 human women) were obtained. The pressure-diameter relations of the proper hepatic arteries were measured on biomechanical test equipment to calculate the incremental elastic modulus (Einc), pressure-strain elastic modulus (Ep), volume elastic modulus (Ev), and compliance. Each sample was sliced into 5-µm frozen sections and stained with hematoxylin-eosin. RESULTS: There were significant differences in Einc (F=10.24; P = .001), Ep (F=3.75; P = .001), and Ev (F=3.41; P = .002) of the proper hepatic arteries of female, male, and gonadectomized pigs; females had the lowest elastic modulus and the gonadectomized group had the highest (P < .01). There was a significant difference in compliance of the porcine proper hepatic arteries between the sexes, highest in the female group and lowest in the gonadectomized group (P < .01). No difference in the elastic modulus and compliance of the proper hepatic artery between the male pig and the human man. There was no difference between the female pig and the human woman. CONCLUSIONS: There were differences in the biomechanical properties of the proper hepatic arteries of the female, male, and gonadectomized pigs. The biomechanical properties of the human men/women proper hepatic artery match those of the porcine male/female hepatic artery. The correlation between sex and biomechanical properties of the proper hepatic artery in pigs could imply that a pig of the same sex should be chosen for pig-to-human liver xenotransplant.

Morphological and biomechanical remodeling of the hepatic portal vein in a swine model of portal hypertension.

OBJECTIVES: To obtain the morphological and biomechanical remodeling of portal veins in swine with portal hypertension (PHT), so as to provide some mechanical references and theoretical basis for clinical practice about PHT. METHODS: Twenty white pigs were used in this study, 14 of them were subjected to both carbon tetrachloride- and pentobarbital-containing diet to induce experimental liver cirrhosis and PHT, and the remaining animals served as the normal controls. The morphological remodeling of portal veins was observed. Endothelial nitric oxide synthase expression profile in the vessel wall was assessed at both mRNA and protein level. The biomechanical changes of the hepatic portal veins were evaluated through assessing the following indicators: the incremental elastic modulus, pressure-strain elastic modulus, volume elastic modulus, and the incremental compliance. RESULTS: The swine PHT model was successfully established. The percentages for the microstructural components and the histological data significantly changed in the experimental group. Endothelial nitric oxide synthase expression was significantly downregulated in the portal veins of the experimental group. Three incremental elastic moduli (the incremental elastic modulus, pressure-strain elastic modulus, and volume elastic modulus) of the portal veins from PHT animals were significantly larger than those of the controls (P < 0.05), whereas the incremental compliance of hepatic portal vein decreased. CONCLUSIONS: Our study suggests that the morphological and biomechanical properties of swine hepatic portal veins change significantly during the PHT process, which may play a critical role in the development of PHT and serve as potential therapeutic targets during clinical practice.

Morphological and biomechanical remodelling of the hepatic artery in a swine model of portal hypertension.

OBJECTIVES: To obtain the biomechanical and morphological remodelling of hepatic arteries in swine with portal hypertension. METHODS: A number of 20 white pigs was used, of which 14 were subjected to liver cirrhosis and portal hypertension (PHT) induced by carbon tetrachloride and pentobarbital; the rest were used as the control group. The biomechanical remodelling of the hepatic arteries was measured, namely, the incremental elastic modulus (E inc), pressure-strain elastic modulus (E p), volume elastic modulus (E v), the incremental compliance (C), the opening angle and the stained microstructural components of the vessels. RESULTS: The percentages for the microstructural components and the histologic data significantly changed in the experimental group, three incremental elastic moduli (E inc, E p, and E v) of the experimental group were significantly larger than those of the control group (P < 0.05); the compliance of hepatic arteries decreased greatly (P < 0.05) too. The opening angle (OA) was considerably larger than that of control group (P < 0.05). CONCLUSIONS: The study suggests that the morphological and biomechanical properties of swine hepatic arteries have changed significantly during the process of portal hypertension and that from biomechanical aspects, the hepatic arteries have also suffered from extensive remodelling, which in turn deteriorates the existing portal hypertension.

Calcitonin gene-related peptide enhances CREB phosphorylation and attenuates tau protein phosphorylation in rat brain during focal cerebral ischemia/reperfusion.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. Exogenous CGRP could increase the cerebral blood flow significantly and protect the ischemic neurons, but its mechanism is not entirely clear. The effect of CGRP on the expressions of CREB and tau in the ipsilateral parietal cortex were detected in focal cerebral ischemia/reperfusion model. The expression of CREB mRNA decreased in ischemia/reperfusion group (I/R group) compared with that of the sham operation group, and it got highest in CGRP group. CREB expression was lesser in I/R group than sham group, but it became more in CGRP group than I/R group. Phospho-CREB became more in I/R group, and it got most in CGRP group in the cortex. No significant difference was observed on Tau mRNA expression in all the groups. The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat parietal cortex were significantly higher in I/R group than sham group. CGRP significantly inhibited tau hyperphosphorylation and the level of total tau also significantly reduced in CGRP group than that in I/R group. CGRP can upregulate the expression of CREB and phospho-CREB and attenuate the level of tau hyperphosphorylation in the ischemic neurons of the parietal cortex during focal cerebral ischemia/reperfusion. Phosphorylating CREB and inhibiting tau phosphorylation are probably involved in the mechanism of protective effect of CGRP to ischemic neurons.

Cyclic-AMP response element binding protein and tau are involved in the neuroprotective mechanisms of nerve growth factor during focal cerebral ischemia/reperfusion in rats.

Nerve growth factor (NGF) has protective and therapeutic effects after cerebral ischemic injury. However, its mechanism of action is not clear. We explored the protective mechanism of exogenous NGF on rat hippocampal neurons after focal cerebral ischemia/reperfusion. Changes were detected in the expression of cyclic-adenosine monophosphate (AMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA), CREB protein, phosphorylated CREB, tau mRNA, total tau protein and the state of phosphorylation of tau protein at the serine 199/202 site. NGF treatment significantly increased the expression of CREB mRNA, CREB and phosphorylated CREB in the hippocampal CA1 region. NGF alleviated the level of phosphorylation of tau and the expression level of total tau. It is possible that the protective effect of NGF on the ischemic neuron was due to the activation of transcription and translation of CREB, the reduction in the level of phosphorylation of tau protein, and the activation of a series of signal pathways.

Expression of calcitonin gene-related peptide in anterior and posterior horns of the spinal cord after brachial plexus injury.

This study shows the expression pattern of calcitonin gene-related peptide (CGRP) in the anterior and posterior horns of the spinal cord after brachial plexus injury. The animals were divided into three injury groups: group 1, right C(7) anterior root avulsion; group 2, right C(7) anterior root avulsion and cut right C(5)-T(1) posterior roots; and group 3, right C(7) anterior root avulsion plus right hemitransection between the C(5) and C(6) segments of the spinal cord. These animals were killed at 1, 3, 7 and 14 days after injury. In the anterior horn of all three injured groups, the expression of CGRP increased progressively from day 1 to day 7 (p<0.05), peaked on day 7, and then began to decrease slowly. In the posterior horn of all three injured groups, the expression of CGRP decreased gradually from day 1 to day 14 after the operation and was significantly lower on day 14 compared to day 1. At each time point (days 1, 3, 7 and 14), the expression of CGRP was the highest in group 1 and the lowest in group 2, with significant differences among the three groups. The CGRP in the anterior horn of the spinal cord was derived from the cell bodies of motor neurons and was possibly involved in repair mechanisms and regeneration after nerve injury. However, the CGRP in the posterior horn was mainly derived from the posterior root ganglion and was possibly associated with the conduction of noxious stimulation.

The impact of age on incremental elastic modulus and incremental compliance of pig hepatic portal vein for liver xenotransplantation.

BACKGROUND: Pigs are currently considered the most likely source of organs for human xenotransplantation because of anatomical and physiological similarities to humans, and the relative ease to be bred in large numbers. Along with the fast development of the genetic engineering and organ transplant immunity medical science, the research of liver xenotransplantation suffers the very big valuing in recent years. Whether the livers from different species after transplanting can perform the normal function, depends on the function regeneration and lucid rates of hepatic portal vein. The objective of this study was to investigate the age effect on biomechanical properties of pig hepatic portal vein to pave the way for seeking a reliable biomaterial for future pig-to-human liver xenotransplantation. METHODS: The biomechanical remodelling of the hepatic portal vein of pigs for 1,2,3,4,5 and 6 months (n = 6 per month) were measured in this study. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The incremental modulus (Einc), the longitudinal incremental modulus (Ep), the circumferential incremental modulus (Ev), incremental compliance (C) and wall thickness were calculated based on the recorded pressure-diameter curves from experimental data. RESULTS: The incremental modulus, pressure strain modulus and the volume modulus of the pig hepatic portal vein increases with the age increased (P < 0.01), while the compliance decreased with the increasing of the age (P < 0.01). CONCLUSIONS: Our present study suggests that the biomechanical properties of the pig hepatic portal vein are age dependent, the pig hepatic portal vein with biomechanical properties that match those of human hepatic portal vein should be chosen for liver xenotransplantation.

Quantitative analysis of the microstructure of human umbilical vein for assessing feasibility as vessel substitute.

We explored the feasibility of human umbilical vein (HUV) as a small-caliber vessel substitute. HUVs of 50 fetuses were collected on spontaneous miscarriage or labor with the pregnant women's permission. Gestational age ranged 24-42 weeks, and parturients were 20-30 years old. Each sample was sliced into 5 mum frozen transverse sections and stained with hematoxylin-eosin (HE), Weigert, aniline blue, and orange yellow G. The geometric morphological indexes and microstructural component were measured by a computer image analysis system. The media thickness was 0.186, 0.203, 0.237, 0.264, and 0.268 mm at 24-27, 28-32, 33-36, 37-40, and 41-42 weeks, respectively (F = 133.35, p < 0.01); diameters were 1.861, 1.962, 2.303, 2.464, and 2.465 mm (F = 37.35, p < 0.01), respectively. The media thickness and diameter of HUVs increased with gestational age. The elastin content of media increased at 24-40 weeks, but the collagen content and collagen/elastin (C/E) ratio decreased. Elastin content in the proximal segment was higher than in the distal segment [10.16, 6.36 Aa%, (Aa% is the unit of relative content, ie, the ratio of absolute areas to the total tested area of smooth muscle, collagen and elastin in the vascular wall) F = 5.77-12.3, p < 0.05], with the collagen to elastin (C/E) ratio increasing from the proximal to the distal segment (F = 7.63-13.4, p < 0.05). Our results suggest that the microstructural component of HUVs (2.0-3.0 mm caliber) at 37-40 weeks of gestation was similar to that of the small-caliber arteries and had moderate amounts of collagen and elastin and good elasticity, i.e., a good C/E ratio; therefore, HUV may be a substitute for small-caliber arteries (e.g., brachial, ulnar, radial, right coronary, anterior tibial, and posterior tibial). HUV is one of several graft materials that may be used when autogenous saphenous vein is absent or inadequate.

Biomechanical properties of ascending aorta and pulmonary trunk in pigs and humans.

BACKGROUND: This study aims to obtain the biomechanical properties of ascending aorta and pulmonary trunk between healthy humans and pigs of different months, so as to provide necessary biomechanical experimental basis for anastomosing blood vessel in pig-to-human heart xenotransplantation. METHODS: Ascending aorta and pulmonary trunks of the six deceased donors (male 4, female 2) and 42 Chinese Hubei white pigs aged 1-7 months were performed biomechanical test. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The elastic properties of the blood vessels were obtained by curve from experimental data. RESULTS: The biomechanical material constant of ascending aorta and pulmonary trunk of pigs did not increase with the increase of age (F = 14.569, P = 0.126). The biomechanical material constant of humans was basically similar to that of pigs aged 1-7 months (F = 12.264, P = 0.225). The elastic modulus was the biggest in pigs aged 7 months in comparison with that in other ages (F = 27.425, P = 0.032). There was no significant difference of elastic modulus of corresponding blood vessel between humans and pigs of different months (F = 17.328, P = 0.215). CONCLUSIONS: Our present study suggests that there was no significant difference of elastic properties of ascending aorta and pulmonary trunks between humans and pigs. From biomechanical aspects, anastomosis of corresponding ascending aorta and pulmonary trunks in the process of pig-to-human heart xenotransplantation may be feasible.

Biomechanical properties of different segments of human umbilical cord vein and its value for clinical application.

No satisfactory effects have been obtained with the use of synthetic blood vessels (diameter <6 mm) as substitutes for human small arteries or veins for the purpose of clinical vascular reconstruction. Therefore, blood vessels of human origin, for example, umbilical cord blood vessels, with their wide availability, still should be considered. However, little information on biomechanical properties of human umbilical cord blood vessels is available. The objective was to provide a theoretical basis for the clinical application of umbilical cord veins as optional material for small-caliber grafts. This was a nonrandomized, noncontrolled in vitro study. The experiment was conducted in the Laboratory of Medical Biomechanics, Yunyang Medical College. Umbilical cord veins of 20 normal fetuses of spontaneous labor were collected by the Department of Obstetrics and Gynecology, Taihe Hospital in Shiyan City, Hubei Province. The fetuses aged 37-40 weeks, and the parturients were 20-30 years old. Umbilical cord veins of the 20 fetuses were used and the placental ends were treated as proximal ends while the fetal ends as distal ends. The fetal ends were divided into three segments: proximal, middle, and distal segments. The relationship between pressure of umbilical cord veins segments and the diameters was measured on the biomechanical experiment stand for soft tissues, and then the elastic modulus was calculated. The materials were transversely extracted, refrigerated, and sliced up before HE staining. The geometrical morphology indexes were measured by a computer image analysis system (Leica-Q500IW). The main outcome measures were: incremental elastic modulus (E(inc)), pressure-strain elastic modulus (E(p)), volume elastic modulus (E(v)), diameter, and wall thickness of the veins. E(inc), E(p), and E(v) of umbilical cord veins of proximal, middle, and distal segments increased with the pressure elevated. The three kinds of elastic modulus of proximal segments (E(inc): 26.98 +/- 3.21, E(p): 16.58 +/- 2.12, E(v): 8.31 +/- 2.35) were all lower than those of distal segments (E(inc): 33.20 +/- 4.21, E(p): 119.45 +/- 2.87, E(v): 9.71 +/- 1.32) (F = 95.74-126.52, p < 0.05), and a tendency to increase was shown from proximal segments to distal segments. Media thickness [(0.30 +/- 0.05)] mm, (0.24 +/- 0.03) mm] and the diameters [(3.07 +/- 0.12) mm, (2.30 +/- 0.13) mm] decreased gradually from proximal to distal segments (F = 12.76, p < 0.01). It is feasible to use umbilical cord veins as substitutes for the transplantation of small-caliber arteries in terms of basic biomechanical properties. On vascular grafting, different segments of umbilical cord veins should be chosen cautiously so that the biomechanical characteristics of umbilical cord vein grafts could be in accordance with those of host to increase the long-term patency rate of transplanted blood vessels.