ANTEROVENTRAL WALL OF THE THIRD VENTRICLE AND DORSAL LAMINA TERMINALIS: HEADQUARTERS FOR CONTROL OF BODY FLUID HOMEOSTASIS?

1. The subfornical organ, median preoptic nucleus and the organum vasculosum of the lamina terminalis (OVLT) are a series of structures situated in the anterior wall of the third ventricle and form the lamina terminalis. The OVLT and ventral part of the median preoptic nucleus are part of a region known as the anteroventral third ventricle region.
2. Data from many laboratories, using techniques ranging from lesions, electrophysiology, neuropharmacology, Fos expression, immunohistochemistry and receptor localization, indicate that the tissue in the lamina terminalis plays a major role in many aspects of body fluid and electrolyte balance.
3. The subfornical organ and OVLT lack the blood-brain barrier and detect alterations in plasma tonicity and the concentrations of circulating hormones such as angiotensin II and possibly atrial natriuretic peptide and relaxin.
4. This information is then integrated within the lamina terminalis (probably in the median preoptic nucleus) with neural signals from other brain regions. The neural output from the lamina terminalis is distributed to a number of effector sites including the paraventricular (both parvo- and magno-cellular parts) and supraoptic nuclei and influences vasopressin secretion, water drinking, salt intake, renin secretion, renal sodium excretion and cardiovascular regulation.     

Oral rehydration solutions in gastroenteritis before and after admission to hospital

Two recent studies published in this Journal draw attention to deficiencies in treatment of children with acute infectious diarrhoea in Australia.^1,2 There is now no doubt that use of correctly constituted oral rehydration solutions provides optimal therapy for affected children unless circulation is compromised, vomiting is more than average, or complicating disorders are present. In the vast majority of cases, these complications do not occur. A high proportion of the childhood population experiences gastroenteritis at some time. It is known that 50% of Melbourne children require medical attention for rotavirus infection alone during their first 3 years of life, although less than 5% require admission.     

Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy

BACKGROUND: Previous studies suggested granulocyte-macrophage-colony stimulating factor (GM-CSF) might be beneficial for radiotherapy-induced mucositis. This trial examined the efficacy of GM-CSF in reducing mucositis of the oral cavity and/or oropharynx compared with conventional treatment. METHODS: Mucositis, documented by a five-grade scale, was defined in patients with tumors of the head-neck. Centers were allowed to use their own preferred fractionation regimen. Randomization to treatment was decided before radiotherapy. Treatment with GM-CSF 4 microg/kg/d subcutaneous, started when patients displayed a mucositis score > or = 1.5. RESULTS: Ninety-two patients entered the study according to intention-to-treat principle. Twenty did not reach a mucositis index of 1.5. Sixty-one patients were included in the statistical analysis. Forty-five percent of the patients randomized to receive GM-CSF had a significant reduction of the mucositis more than one grade compared to 9% of the conventional treated. CONCLUSIONS: In severe mucositis, GM-CSF is more effective than conventional treatment.     

Tetramer binding and secretion of interferon-gamma in response to antigenic stimulation are compatible with a range of affinities of MHC:TCR interaction and distinct programs of cytotoxic T-lymphocyte activation

Tetramer staining and detection of IFN-gamma secretion in response to specific stimulation are widely used to quantify and isolate specific T-cells. However, it remains unclear how these assays reflect different functional outcomes of T-cell triggering with MHC:peptide ligands. An immunogenic EBV-derived A11-restricted CTL peptide epitope and its partially agonistic analogue trigger different programs of activation induced cell death (AICD) in specific CTLs. In this study we analysed a panel of CTL clones, bulk CTL cultures and PBMCs isolated from HLA A11-positive EBV-infected individuals for their ability to bind tetrameric complexes assembled with either of the two peptides and correlated tetramer binding with the activity of the peptides in functional assays. This analysis demonstrates that specific tetramer staining and secretion of IFN-gamma are compatible with at least two activation programs in CTLs. One of these programs corresponds to full-scale CTL activation and death of a proportion of activated T-cells in a Fas-dependent manner. In contrast, the alternative program is characterized by selective induction of IFN-gamma and TNF-alpha, absence of proliferative response and Fas-independent cell death. These findings may have important implications for the evaluation of data obtained with MHC:peptide tetramers and IFN-gamma secretion assays, especially in experimental systems with extensive antigenic variability.     

The use of on-line and off-line chromatographic extraction techniques coupled with mass spectrometry for support of in vivo and in vitro assays in drug discovery

We have investigated various sample chromatographic extraction and sample preparation methods for liquid chromatography mass spectrometry analysis in order to increase the throughput of various in vivo and in vitro assays in support of drug discovery. The results indicated that direct plasma injection, although certainly faster than conventional protein precipitation for sample preparation, had problems associated with column longevity and overall robustness. Frequently a single study could not be completed without column replacement. On-line solid phase extraction, on the other hand, compared well with off-line solid phase extraction, using our LC extraction column design, as contamination of the extraction column was minimized by back flushing using the Gilson syringe pump. Finally, on-line solid phase extraction for support of Caco-2 permeability studies worked very well for both single components and mixtures as the matrix was much simpler, presenting fewer contamination problems.     

Respiratory function after repair of congenital diaphragmatic hernia

Respiratory function studies were carried out in 22 infants who had successful repair of diaphragmatic herniae of the Bochdalek type. Thoracic gas volume was initially reduced in only 3 of these, but subsequent studies showed that improvement occurred. There were no consistent abnormalities in either dynamic compliance or mean pulmonary conductance. This is evidence that there is rapid adaptation which compensates for any alteration in the parenchymatous tissue in the lungs or abnormalities in the bronchial tree in infants soon after the repair of congenital diaphragmetic herniae. Further studies are necessary to determine the changes in these lungs with growth.     

Specific and non-specific components in the triggering of proliferative and cytotoxic responses of T lymphocytes with different cell density

We hve analyzed the functional behavior of lymphocyte subsets separated on the basis of cell density. Low and high density subpopulations were cultured in FCS, alone or with allogeneic irradiated PBL, and then examined for proliferation and cytotoxic activity against autologous (responder) and allogeneic (stimulator) PHA-induced blasts, K562 and Daudi. In the high density subset proliferation and generation of anti-K562 and anti-Daudi effects were induced by FCS and to higher extent by allospecific stimulation. Exposure to alloantigens induced allospecific cytotoxicity. Autologous PHA blasts were not affected. The results with the low density subset differed. Independently of the type of stimulus imposed, the low density fraction showed little if any proliferation, but its cytotoxic activity was stronger against all targets tested. In some of the experiments, anti-alloblast cytotoxicity was generated in the control cultures. Thus, polyclonal activation induced by FCS triggered in this fraction allospecific cytotoxicity. In this subset, the effect against allogeneic PHA blasts comprised a specific and a non-specific component because autologous PHA blasts were also lysed. Limiting dilution analysis involving allostimulation showed higher frequency of cytotoxic precursors in the low density subset. Split minicultures were tested for lysis of auto- and allogeneic blasts. Alloreactive cultures that did not lyse the autologous target were more frequent in the cultures initiated with the high density cells. There was no conclusive evidence for the existence of autoreactive cultures that did not lyse the allogeneic blasts.     

常咯啉在实验性心律失常狗的药代动力学-药效动力学分析

用Harris冠脉结扎法诱发的心律失常狗研究常咯啉药代动力学-药效动力学。7只狗按83.33μg·kg^-1·min^-1静脉滴注60min,在给药期间和停药后不同时间记录ECG及测定血药浓度。C-T数据用药代程序计算药代参数;药效数据用药代-药效同步分析模型计算药效动力学参数,K₁₀, T_1/2,Vd,Cl分别为0.0087min^-1,78.03min,40.55ml·kg^-1和0.421ml·kg^-1·min^-1;K_eO和Ce(50)分别为0.0048min^-1和2.01μg·ml^-1.