Changes in T .lymphocyte subsets after severe traumatic brain inJury

BACKGROUND： Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE： To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN： A comparative observation. SETTINGS： Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS： All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score （GCS） was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group （GCS ranged 14- 15 points）, including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS： （1） The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. （2） The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES： Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS： Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. （1） Changes of T lymphocyte subsets： At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group （t =2.77 - 3.26, P 〈 0.01）, and began to recover at 7 days, which were significantly different from those in the control group （t = 2.06 - 2.24, P 〈 0.05）, and generally recovered to the normal levels at 14 days （P 〉 0.05）. （2） Conditions of pulmonary infections： At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% （22/30）, 0, x2=37.29, P 〈 0.01]. CONCLUSION： Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period （within 7 days）, and they are easily to be accompanied by pulmonary infections.     

Crystal and molecular structure of l-valyl-l-lysine hydrochloride

l -Valyl-l -lysine hydrochloride, C₁₁N₃O₃H₂₃ HCl, crystallizes in the monoclinic space group P2, with a = 5.438(5), b = 14.188(5), c = 9.521(5) Å, β= 95.38(2)° and Z = 2. The crystal structure, solved by direct methods, refined to R = 0.036, using full matrix least-squares method. The peptide exists in a zwitterionic form, with the N atom of the lysine side-chain protonated. The two γ-carbons of the valine side-chain have positional disorder, giving rise to two conformations, χ¹¹₁= -67.3 and 65.9°, one of which (65.9°) is sterically less favourable and has been found to be less popular amongst residues branching at β-C. The lysine side-chain has the geometry of g^? tgt, not seen in crystal structures of the dipeptides reported so far. Interestingly, χ³₂ (63.6°) of lysine side-chain has a gauche⁺ conformation unlike in most of the other structures, where it is trans. The neighbouring peptide molecules are hydrogen bonded in a head-to-tail fashion, a rather uncommon interaction in lysine peptide structures. The structure shows considerable similarity with that of l -Lys-l -Val HO in conformational angles and H-bond interactions [4].     

Pathophysiological aspects of brain edema

Summary Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In theischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthday     

Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

背根神经节内P物质、降钙素基因相关肽免疫阳性神经元与阴茎包皮系带感觉信息的传递

目的:探讨背根神经节(DRG)内P物质(SP)、降钙素基因相关肽(CGRP)免疫阳性神经元与阴茎包皮系带感觉信息传递之间的关系。方法:通过荧光金(FG)逆行标记对大鼠阴茎包皮系带内神经末梢的来源作追踪定位,并结合SP、CGRP免疫荧光标记法,研究大鼠DRG内FG标记阳性神经元中SP、CGRP免疫阳性神经元的形态和分布。结果:FG逆行标记结果发现,大鼠阴茎包皮系带内的神经末梢起源于第6腰髓对应的背根神经节(L6-DRG)和第1骶髓对应的背根神经节(S1-DRG)的神经元。对这些神经元分别作SP、CGRP免疫荧光标记后发现,标记细胞大小不等,分别呈深红色和深绿色,沿神经束成行排列或散在分布。FG/SP、FG/CGRP双标记阳性细胞均为中小型,其数量分别占FG逆行标记阳性细胞总数的1/3和1/2,FG/SP/CGRP三标记阳性细胞占FG逆行标记阳性细胞总数的1/5。结论:大鼠L6-DRG和S1-DRG内的SP、CGRP免疫阳性神经元可能参与阴茎包皮系带感觉信息的传递。     

Parental alcohol use and brain volumes in early- and late-onset alcoholics.

BACKGROUND: Studies have shown that alcoholics have smaller brain volumes than non-alcoholic cohorts, but an effect of family history (FH) of heavy drinking on brain volume has not been demonstrated. We examined the relationship between an FH of heavy drinking and both brain shrinkage as measured by the ratio of brain volumes to intracranial volume (ICV) as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. METHODS: With T1-weighted resonance imaging, we measured ICV, brain volume, and white and gray matter volume in adult treatment-seeking late-onset and early-onset alcoholics with either a positive or a negative FH of heavy alcohol use, and in healthy control subjects. We also calculated brain shrinkage using a ratio of soft tissue volumes to ICV. RESULTS: The FH positive alcoholic patients had significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth. Brain shrinkage did not correlate with FH. Late-onset alcoholics showed a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also had significantly lower IQ scores than late-onset FH negative patients, and IQ scores were correlated with ICV. CONCLUSIONS: These data provide evidence that parental alcohol use might increase risk for alcoholism in offspring in part by a genetic and/or environmental effect that might be related to reduced brain growth.