Ginger-Degraded Collagen Hydrolysate Exhibits Antidepressant Activity in Mice.

Collagen is the most abundant protein in animals. Collagen hydrolysate has been found to have multiple functions in the skin, bones, joints, muscles, and blood vessels. Recently, it has been reported that the low molecular weight fraction of collagen hydrolysate exhibited anxiolytic activity, suggesting that collagen peptides affect brain functions. In the present study, we found that oral administration of ginger-degraded collagen hydrolysate (GDCH) significantly decreased depression-like behavior in a forced swim test, suggesting that GDCH exhibited antidepressant activity in mice. The antidepressant activity of GDCH was abolished by pre-treatment with an antagonist of the dopamine receptor, but not treatment with a serotonin receptor antagonist. GDCH significantly increased gene expression of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the hippocampus, molecules that affect the differentiation and survival of neurons, relative to that in the control condition. Meanwhile, there were no changes in the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3, major factors related to depression-like behavior. We also found that GDCH exhibited antidepressant activity in corticosterone-administered mice in a model of stress. In addition, GDCH increased GDNF and CNTF expression in the stressed condition, suggesting that mechanisms of the antidepressant activity of GDCH were the same in unstressed and stressed conditions. These results imply that GDCH exhibits antidepressant activity in unstressed and stressed conditions in mice. The upregulation of neurotrophic genes in the hippocampus may contribute to the reduction of depression-like behavior via a dopamine signal pathway modulated by GDCH.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels.

OBJECTIVE: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. METHODS: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. RESULTS: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. CONCLUSIONS: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury.

PURPOSE: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. METHODS: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. RESULTS: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. CONCLUSION: Our findings provided evidence for the clinical usage of HBO treating brain damages.

The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury

Abstract Purpose: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. Methods: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Results: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. Conclusion: Our findings provided evidence for the clinical usage of HBO treating brain damages.

Effect of Electro-Acupuncture on Neuroplasticity of Spinal Cord-Transected Rats.

BACKGROUND This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT). MATERIAL AND METHODS A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T10-T11 vertebral levels. Then, EA group rats received EA treatment. Reverse transcription polymerase chain reaction was used to detect NTFs and receptors at the mRNA level. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the expression of NTFs and their receptors. Basso, Beattie, Bresnahan (BBB) scores and cortical somato-sensory evoked potentials (CSEP) were evaluated to assess the recovery of motor and sensory functions. We also measured BDA (Biotinylated dextran amine) axonal tracing, CGRP (Calcitonin gene-related peptide), GAP-43 (Growth-associated protein), and synaptophysin immunohistochemistry (IHC). RESULTS EA treatment led to obvious improvement in hindlimb locomotor and sensory functions. CNTF, FGF-2, and TrkB mRNA were significantly upregulated, while NGF, PDGF, TGF-b1, IGF-1, TrkA, and TrkC mRNA were concomitantly downregulated in the caudal spinal segment (CSS) following EA. Immunohistochemistry demonstrated an increased number of CGRP fibers, GAP-43, and synaptophysin profiles in the CSS in the EA rats. CONCLUSIONS EA may promote the recovery of neuroplasticity in rats subjected to SCT. This could be attributed to the systematic regulation of NTFs and their receptors after EA.

Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation.

Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. The oral gingival epithelium is exposed to multiple noxious stimuli, including heat and acids derived from endogenous and exogenous substances; however, whether gingival epithelial cells (GECs) express TRPV1 is unknown. We show that both TRPV1 mRNA and protein are expressed by GECs. Capsaicin, a TRPV1 agonist, elevated intracellular Ca(2+) levels in the gingival epithelial cell line, epi 4. Moreover, TRPV1 activation in epi 4 cells accelerated proliferation. These responses to capsaicin were inhibited by a specific TRPV1 antagonist, SB-366791. We also observed GEC proliferation in capsaicin-treated mice in vivo. No effects were observed on GEC apoptosis by epithelial TRPV1 signaling. To examine the molecular mechanisms underlying this proliferative effect, we performed complementary (c)DNA microarray analysis of capsaicin-stimulated epi 4 cells. Compared with control conditions, 227 genes were up-regulated and 232 genes were down-regulated following capsaicin stimulation. Several proliferation-related genes were validated by independent experiments. Among them, fibroblast growth factor-17 and neuregulin 2 were significantly up-regulated in capsaicin-treated epi 4 cells. Our results suggest that functional TRPV1 is expressed by GECs and contributes to the regulation of cell proliferation.

Association between neurotrophin 4 and long-chain polyunsaturated fatty acid levels in mid-trimester amniotic fluid.

The omega-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) and the omega-6 LCPUFA arachidonic acid (AA) are essential nervous system components that increase in concentration throughout gestation. The neurotrophins, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) are small basic peptides crucial for fetal brain development. The DHA supplementation during pregnancy has been suggested to enhance neural development. We evaluated whether amniotic fluid DHA and AA concentrations correlated with intra-amniotic neurotrophin levels. Amniotic fluid, obtained at 15 to 19 weeks gestation from 62 women, was tested for BDNF, NGF, NT3, and NT4 by enzyme-linked immunosorbent assay. Concentrations of DHA and AA, and saturated and monounsaturated fatty acids, were determined by gas chromatography. Associations were analyzed by the Spearman rank correlation test. Median levels of AA and DHA were 2.3% and 1.3% of the total intra-amniotic fatty acids, respectively. Median neurotrophin levels (pg/mL) were 36.7 for NT3, 26.8 for BDNF, 5.2 for NT4, and 0.8 for NGF. Intra-amniotic NT4 and BDNF levels were correlated (P = .0016), while NT3 and NGF levels were unrelated to each other or to BDNF or NT4. Only NT4 was positively correlated with amniotic fluid DHA (P < .0001) and AA (P = .0003) concentrations. There were no associations between DHA, AA, or any neurotrophin and maternal age, gestational age at time of amniocentesis, amniocentesis indication, parity, or gestational age at delivery. Elevations in intra-amniotic NT4 with increasing levels of DHA and AA suggest that these LCPUFAs may specifically influence the extent of NT4-mediated fetal brain neurogenesis.

Biomarkers of brain damage in preterm infants.

OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.

Neurological biomarkers in the perioperative period.

The rapid detection and evaluation of patients presenting with perioperative neurological dysfunction is of great clinical relevance. Biomarkers have been defined as biological molecules that can be used as an indicator of new onset or progression of a biological process or effect of treatment. Biomarkers have become increasingly important in this setting to supplement other modalities of diagnosis such as EEG, sensory- or motor-evoked potential, transcranial Doppler, near-infrared spectroscopy, or imaging methods. A number of neuro-proteins have been identified and are currently under investigation for potential to provide insights into injury severity, outcome, and the ability to monitor cellular damage and molecular events that occur during neurological injury. S100B is a protein released by glial cells and is considered a marker of blood-brain barrier dysfunction. Clinical studies in patients undergoing cardiac and non-cardiac surgery indicate that serum levels of S100B are increased intraoperatively and after operation. The neurone-specific enolase has also been extensively investigated as a potential marker of neuronal injury in the context of cardiac and non-cardiac surgery. A third biomarker of interest is the Tau protein, which has been linked to neurodegenerative disorders. Tau appears to be more specific than the previous two biomarkers since it is only found in the central nervous system. The metalloproteinase and ubiquitin C terminal hydroxylase-L1 (UCH-L1) are the most recently researched markers; however, their usefulness is still unclear. This review presents a comprehensive overview of S100B, neuronal-specific enolase, metalloproteinases, and UCH-L1 in the perioperative period.

Determination of the biological variation of S100ß and lactate dehydrogenase in disease-free patients with malignant melanoma.

BACKGROUND: Biological variation is important for determining analytical goals and for establishing the magnitude of change between two consecutive measurements. The aim of this study was to determine the biological variation for S100ß and lactate dehydrogenase in patients diagnosed with malignant melanoma but without evidence of disease recurrence. METHODS: The biological variation of S100ß and lactate dehydrogenase was estimated from a mean of four consecutive measurements in 32 patients diagnosed with malignant melanoma but without evidence of disease recurrence, 3 months after tumor resection or 4 months after finishing adjuvant treatment. The mean sampling interval was 3 months. RESULTS: Mean concentrations of S100ß and lactate dehydrogenase were 0.0557 µg/L and 6.3 µkat/L, respectively. Between-run analytical variation was 3.5% at 0.181 µg/L for S100ß and 3.5% at 2.83 µkat/L for lactate dehydrogenase. Biological variations obtained for S100ß and lactate dehydrogenase were 14.2% and 8.2%, respectively. The analytical goals (defined as 50% of biological variation) were 7.1% for S100ß and 4.1% for lactate dehydrogenase. CONCLUSIONS: The estimation of biological variation allows us to calculate analytical goals and reference change values. These are necessary tools for the correct interpretation of serial measurements in patient follow-up.

In vitro S100B secretion is reduced by apomorphine: effects of antipsychotics and antioxidants.

Astrocytes express dopamine receptors and respond to dopamine stimulation. However, the role of astrocytes in psychiatric disorders and the effects of antipsychotics on astroglial cells have only been investigated recently. S100B is a glial-derived protein, commonly used as a marker of astroglial activation in psychiatric disorders, particularly schizophrenia. We investigated S100B secretion in three different rat brain preparations (fresh hippocampal slices, C6 glioma cells and primary astrocyte cultures) exposed to apomorphine and antipsychotics (haloperidol and risperidone), aiming to evaluate, ex vivo and in vitro, whether dopamine activation and dopaminergic antagonists modulate astroglial activation, as measured by changes in the extracellular levels of S100B. The serum S100B elevation observed in schizophrenic patients is not reflected by the in vitro decrease of S100B secretion that we observed in hippocampal slices, cortical astrocytes and C6 glioma cells treated with apomorphine, which mimics dopaminergic hyperactivation. This decrease in S100B secretion can be explained by a stimulation of D2 receptors negatively coupled to adenyl cyclase. Antipsychotic medications and antioxidant supplementation were able to prevent the decline in S100B secretion. Findings reinforce the benefits of antioxidant therapy in psychiatric disorders. Based on our results, in hippocampal slices exposed to apomorphine, it may be suggested that antipsychotics could help to normalize S100B secretion by astrocytes.

[Markers of brain injury in non-invasive biological fluids]. / Markers of brain injury in non-invasive biological fluids.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS).

The effect of long-term lactobacilli (lactic acid bacteria) enteral treatment on the central nervous system of growing rats.

The aim of this study was to explore the relationship between consumption of large doses of lactic acid bacteria (LAB) and the behaviour and brain morphobiochemistry of normal growing rats. Four groups of rats were treated with LAB cultures twice daily for 6 months. The control group received 1 ml of saline per treatment, while two experimental groups received 1 ml of living bacteria (Lactobacillus plantarum and Lactobacillus fermentum, respectively) and the remaining group received a heat-treated (inactivated) L. fermentum culture. After 2 and 6 months of treatment, respectively, eight animals from each group were sacrificed, and specimens were taken for further analyses. The behaviour of the rats was evaluated five times in an open-field test at monthly intervals throughout the study. Lactobacilli treatment for 2 months induced changes in the motoric behaviour of the rats. The concentration of the astrocytesoluble and filament glial fibrillary acidic protein (GFAP) decreased in the posterior part of the hemispheres, including the thalamus, hippocampus and cortex of the rats treated with L. fermentum. A greater decrease in filament GFAP (up to 50%) was shown in the group receiving the live form of L. fermentum. In contrast, the GFAP in the live L. plantarum-treated group increased, showing elevated levels of the soluble and filament forms of GFAP in the posterior part of the hemispheres. A 60-66% decrease in the amount of the astrocyte-specific Ca-binding protein S-100b was shown in the posterior parts of the hemispheres and in the hindbrain of rats given LAB for 2 months. Prolonged feeding with LAB for 4 months up to full adulthood led to a further decrease in astrocyte reaction, reflected as an additional decrease in the amount of soluble GFAP and locomotor activity in all experimental groups. The changes in filament GFAP and S-100b appeared to disappear after prolonged feeding (total of 6 months) with LAB. In summary, LAB dietary treatment affected the ontogenetic development of the astrocytes, with the highest intensity observed in the early stages of rat development. It can be postulated that LAB treatment may play a preventive role in neurological diseases by decreasing astrocyte reaction and, consequently, lowering locomotor activity.

Successful elimination of non-neural cells and unachievable elimination of glial cells by means of commonly used cell culture manipulations during differentiation of GFAP and SOX2 positive neural progenitors (NHA) to neuronal cells.

BACKGROUND: Although extensive research has been performed to control differentiation of neural stem cells - still, the response of those cells to diverse cell culture conditions often appears to be random and difficult to predict. To this end, we strived to obtain stabilized protocol of NHA cells differentiation - allowing for an increase in percentage yield of neuronal cells. RESULTS: Uncommitted GFAP and SOX2 positive neural progenitors - so-called, Normal Human Astrocytes (NHA) were differentiated in different environmental conditions to: only neural cells consisted of neuronal [MAP2+, GFAP-] and glial [GFAP+, MAP2-] population, non-neural cells [CD44+, VIMENTIN+, FIBRONECTIN+, MAP2-, GFAP-, S100beta-, SOX2-], or mixture of neural and non-neural cells.In spite of successfully increasing the percentage yield of glial and neuronal vs. non-neural cells by means of environmental changes, we were not able to increase significantly the percentage of neuronal (GABA-ergic and catecholaminergic) over glial cells under several different cell culture testing conditions. Supplementing serum-free medium with several growth factors (SHH, bFGF, GDNF) did not radically change the ratio between neuronal and glial cells--i.e., 1,1:1 in medium without growth factors and 1,4:1 in medium with GDNF, respectively. CONCLUSION: We suggest that biotechnologists attempting to enrich in vitro neural cell cultures in one type of cells - such as that required for transplantology purposes, should consider the strong limiting influence of intrinsic factors upon extracellular factors commonly tested in cell culture conditions.

S100B Protein concentration in milk-formulas for preterm and term infants. Correlation with industrial preparation procedures.

Human milk S100B protein possesses important neurotrophic properties. However, in some conditions human milk is substituted by milk formulas. The aims of the present study were: to assess S100B concentrations in milk formulas, to verify any differences in S100B levels between preterm and term infant formulas and to evaluate the impact of industrial preparation at predetermined phases on S100B content. Two different set of samples were tested: (i) commercial preterm (n = 36) and term (n = 36) infant milk formulas; ii) milk preterm (n = 10) and term infant (n = 10) formulas sampled at the following predetermined industrial preparation time points: skimmed cow milk (Time 0); after protein sources supplementation (Time 1); after pasteurization (Time 2); after spray-drying (Time 3). Our results showed that S100B concentration in preterm formulas were higher than in term ones (p < 0.01). In addition, S100B concentrations during industrial preparation showed a significant increase (p < 0.001) at Time 1 followed by a slight decrease (p > 0.05) at Time 2, whereas a significant (p < 0.001) dip was observed at Time 3. In conclusion, S100B showed a sufficient thermostability to resist pasteurization but not spry-drying. New feeding strategies in preterm and term infants are therefore warranted in order to preserve S100B protein during industrial preparation.

Molecular staging for patients with malignant melanoma.

Molecular staging of cancers hold the promise of being more accurate compared with routine histology, particularly with regard to determining regional-nodal status. With newer reverse transcriptase-PCR (RT-PCR)-based assays, sensitivities reported are as high as identifying one cancer cell in a background of a million normal cells. Although this sensitivity is 100-times what the human eye can differentiate under the microscope, the new challenge becomes determining the relevance of this low-volume disease in the regional basin, in particular, the sentinel lymph node (SLN). Patients with melanomas greater than 0.75 mm in tumor thickness participated in a research study that examined their SLNs with routine histology, immunhistochemical staining and a RT-PCR assay based on the tyrosinase probe. A total of 311 patients were involved in the study and patients whose SLN were negative from all three assays for metastatic disease had a good survival, with a 92% disease-free survival (DFS) and a 97% overall survival (OS) regardless of the tumor thickness or the ulceration status of the primary melanoma. Patients upstaged with the RT-PCR assay had a significantly decreased DFS and OS compared with patients who were SLN negative. Patients who had enough tumor burden in the SLN that allowed their metastatic disease to be identified with routine histology had a 48% recurrence rate at 5 years. A recently published meta-analysis confirmed that molecular staging of the SLN in melanoma contains important prognostic information. Micrometastatic disease missed by routine histology in the SLN in melanoma patients is clinically relevant disease. Molecular staging has the potential of providing a more accurate staging in the SLN, for prognostication and directing adjuvant therapies.

A Comparison of 3 tumor markers (MIA, TA90IC, S100B) in stage III melanoma patients.

PURPOSE: There is no consensus regarding the optimal tumor markers for melanoma. We compared 3 tumor markers, TA90-immune complex (TA90IC), melanoma-inhibiting activity (MIA) protein, and S100B protein in Stage III melanoma patients undergoing adjuvant vaccine immunotherapy. EXPERIMENTAL DESIGN: The serum of 75 patients representing 3 prognostic cohorts was assayed for the tumor markers prior to initiating immunotherapy and at 6 follow-up time points. Upper limits of normal for TA90IC, MIA and S100B were set at OD 0.41, 8.5 ng/ml, and 2.5 microg/l, respectively. RESULTS: At least 1 marker became elevated prior to 41 (80 percent) of 51 recurrences. TA90IC was the earliest elevated marker in 29 (57 percent), MIA in 11 (22 percent), and S100B in 4 (8 percent). Multivariate regression analysis revealed that TA90IC was an independent predictor of survival when elevation occurred between 2 weeks and 3 months, whereas MIA was an independent predictor at 4-6 months. In the poor prognostic cohort, mean values for MIA and S100B increased progressively, whereas TA90IC exhibited a parabolic curve. CONCLUSION: In this patient population, TA90IC and MIA were complementary; elevation of the immune complex preceded elevation of the tumor antigen in patients who developed recurrence. Additional studies in populations not receiving vaccine will further clarify the clinical utility of these assays.

Effect of Kangxin Capsule on the expression of nerve growth factors in parietal lobe of cortex and hippocampus CA1 area of vascular dementia model rats.

OBJECTIVE: To observe the effect of Kangxin Capsule (KXC) on the expression of nerve growth factor (NGF) as well as the morphology and amount of nerve synapse in the cortical parietal lobe and hippocampus CA, area of vascular dementia ( VD) model rats. METHODS: The model rats of VD made by photochemical reaction technique were randomly divided into five groups: the model group (MG), the high-dose, middle-dose and low-dose KXC groups (HDG, MDG and LDG), and the Western medicine hydergin control group (WMG). They were treated respectively with distilled water, high, middle and low dosage of KXC suspended liquid, and hydergin for a month. Besides, a blank group consisting of normal (non-model) rats was set up for control (CG). The ultrastructure of nerve synapse in the cortical parietal lobe and hippocampus CA1 area of the rats were observed and its density estimated. The condition of NGF positive neurons in the above-mentioned two regions were also observed by immunohistochemical stain. RESULTS: All the KXC or hydergin treated groups demonstrated a normal amount of nerve synapse with integral structure in the cortical parietal lobe and hippocampus CA, area, which approached that in the CG and was superior to that in the MG. Also, the NGF positive neuron in all the treated groups was much more than that in MG with significant difference ( P<0.01), approaching to that in the CG. CONCLUSION: KXC could elevate the expression of NGF in the cortical parietal lobe and hippocampus CA, area, preserve the number and morphology of synapse, thus to protect the function of nerve system from ischemic injury.

Levels of S100B protein are higher in mature human milk than in colostrum and milk-formulae milks.

BACKGROUND & AIMS: Human milk is believed to contain biological factors involved in the regulation of newborn growth, including brain development. Recently, it has also been shown to contain the calcium-binding S100B protein, regarded as a neurotrophic factor. The present study investigates the concentrations of this protein in colostrum, human milk at different levels of maturation and in milk-formulae. METHODS: Samples for S100B measurements were collected from human colostrum (on day 1 after birth), from transition milk (on post-delivery days 7 and 14) and from mature milk (on day 30 after delivery) in 14 healthy women and from 14 milk-formulae. The S100B protein levels were measured using a commercially available specific immunoluminometric assay. RESULTS: Mean S100B protein levels were significantly higher in mature human milk (117.9+/-36.7 microg/l) than in transition milk at 14 days (106.7+/-38.1 microg/l) and at 7 days (92.7+/-37.8 microg/l), colostrum (74.6+/-37.6 microg/l) or milk-formulae (24.8+/-19.5 microg/l) (P<0.001, for all). A correlation between human milk S100B levels and the gestational age at which samples were obtained was also found (r=0.39; P<0.01). CONCLUSIONS: These findings, possibly related to S100B's neurotrophic role, offers useful information to the investigation of the role of S100B protein in brain maturation.