Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 415 records · Page 23Linked to original sources

PubMed2001

IFN-gamma gene therapy by intrasplenic hepatocyte transplantation: a novel strategy for reversing hepatic fibrosis in Schistosoma japonicum-infected mice.

Liver-targeted gene therapy using hepatocyte as recipient cells has recently been documented to be effective in treatment of numerous hepatic diseases, such as metabolic diseases and liver carcinoma. IFN-gamma elicits antipreliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic satellite cells. To investigate the antifibrogenic response of liver gene therapy mediated by intrasplenic transplantation of gene-modified hepatocytes, normal mouse liver cell line BNL CL.2 cells were transfected with murine IFN-gamma gene (BNL.IFN-gamma) in vitro, and transplanted intrasplenically into Schistosoma japonicum-infected mice. The amounts and distribution of IFN-gamma (which inhibits collagen synthesis), TGF-beta (which stimulates collagen synthesis) and extracellular matrix, including type I and III collagen, were detected. In mice infected with S. japonicum and then treated with BNL.IFN-gamma, an increase of IFN-gamma and decrease of TGF-beta1 were detected at 20 weeks postinfection compared to untreated S. japonicum-infected mice. Immunohistochemical analysis showed that S. japonicum infection induced a marked increase of type I and III collagen synthesis. Whereas, 4 weeks after treatment with BNL.IFN-gamma, net synthesis rates of type I and III collagen were markedly decreased in the liver of infected mice. In addition, a decreased expression of TGF-beta1 and its receptor TGF-betaRII in the liver of BNL.IFN-gamma-treated mice was also observed. Moreover, the decrease in TGF-beta1 and TGF-betaRII protein approximately paralleled the decrease in their mRNA expression, which was detected by RNA dot blotting. The data indicate that intrasplenic transplantation of IFN-gamma gene-modified hepatocyte can be a candidate approach to treat hepatic fibrosis.

Animals↗

PubMed2001

Rubisco activase: an enzyme with a temperature-dependent dual function?

Heat treatment of intact spinach leaves was found to induce a unique thylakoid membrane association of an approximately 40 kDa stromal protein. This protein was identified as rubisco activase. Most of the rubisco activase was sequestered to the thylakoid membrane, particularly to the stroma-exposed regions, during the first 10 min of heat treatment at 42 degrees C. At lower temperatures (38-40 degrees C) the association of rubisco activase with the thylakoid membrane occurred more slowly. The temperature-dependent association of rubisco activase with the thylakoid membrane was due to a conformational change in the rubisco activase itself, not to heat-induced alterations in the thylakoid membrane. Association of the 41 kDa isoform of rubisco activase occurred first, followed by the binding of the 45 kDa isoform to the thylakoid membrane. Fractionation of thylakoid membranes revealed a specific association of rubisco activase with thylakoid-bound polysomes. Our results suggest a temperature-dependent dual function for rubisco activase. At optimal temperatures it functions in releasing inhibitory sugar phosphates from the active site of Rubisco. During a sudden and unexpected exposure of plants to heat stress, rubisco activase is likely to manifest a second role as a chaperone in association with thylakoid-bound ribosomes, possibly protecting, as a first aid, the thylakoid associated protein synthesis machinery against heat inactivation.

Amino Acid Sequence↗

PubMed2001

Analysis of heat-shock transcription factor-DNA binding in Arabidopsis suspension cultures by UV laser crosslinking.

Crosslinking techniques are important in examining protein-DNA interactions in living cells. Formaldehyde and UV light emitted by conventional lamps are the most commonly used crosslinking agents. The crosslinking step is followed by immunoprecipitation of specific protein-DNA adducts, and by analysis and quantification of the co-immunoprecipitated DNA. There are a few reported cases of fruitful in vivo protein-DNA crosslinking experiments, but not in plants. In this report, we analyse the binding of heat-shock transcription factor (HSF) to heat-shock promoters in intact Arabidopsis cells. Efficient protein-DNA crosslinking by irradiation of Arabidopsis suspension culture tissue was achieved using UV laser pulses. In addition, methods for immunoprecipitation and detection of the co-immunoprecipitated DNA are reported. Our results suggest that Arabidopsis HSFs immunoreactive for HSF1 antibodies bind constitutively to the HSP18.2 gene.

Arabidopsis↗

PubMed2001

Purification and cDNA cloning of nitric oxide reductase cytochrome P450nor (CYP55A4) from Trichosporon cutaneum.

Cytochrome P450nor is involved in fungal denitrification as nitric oxide (NO) reductase. Although the heme protein has been known to occur in restricted species of fungi that belong to ascomycotina, we have previously suggested that it would also occur in the yeast Trichosporon cutaneum, which is phylogenetically far from those P450nor-producing ascomycetous fungi. Here we isolated and characterized the heme protein from the basidiomycetous yeast T. cutaneum. P450nor of the yeast (TcP450nor) exhibited properties in terms of catalysis, absorption spectrum and molecular mass that are almost identical to those of its counterparts in ascomycetous fungi. We also isolated and sequenced its cDNA. The predicted primary structure of TcP450nor showed high sequence identities (around 65%) to those of other P450nors, indicating that they belong to the same family. TcP450nor protein cofractionated with cytochrome c oxidase by subcellular fractionation and its predicted primary structure contained an extension on its amino terminus that is characteristic of a mitochondrial-targeting signal, indicating that it is a mitochondrial protein like some of the isoforms of other fungi. On the other hand, TcP450nor was unique in that inducers such as nitrate, nitrite, or NO were not required for its production in the cells. The occurrence of P450nor across the subdivisions of eumycota suggests that P450nor and denitrification are distributed more universally among fungi than was previously thought.

Amino Acid Sequence↗

PubMed2001

Participation of endothelial cells and transformed mesangial cells in remodeling of glomerular capillary loops in Thy-1 nephritis.

The relationship between mesangial cells (MC) and endothelial cells (EC) in the remodeling of glomerular capillary loops was investigated in a rat model of anti-Thy-1 antibody (Ab)-induced glomerulonephritis. Immunohistochemical analysis showed that cells positive for alpha-smooth muscle actin (alpha-SMA) appeared in the mesangial stalks at day three, and had increased in number at day seven, after injection of Thy-1 Ab. Double staining for alpha-SMA and proliferating cell nuclear antigen (PCNA) showed that some MC expressing PCNA were negative for alpha-SMA at day three, but by day seven almost all PCNA-positive MC expressed alpha-SMA. Western blotting for alpha-SMA from isolated glomeruli was negative at day one after injection of Thy-1 Ab, but positive at day seven. Type III collagen appeared at day seven, followed by an increase of EC in the capillary loops, as determined by double immunofluorescent staining for rat endothelial cell antigen-1 (RECA-1) and type III collagen. RECA-1-positive cells increased rapidly in number after day seven and eventually showed the same distribution pattern as that in control rats. Both type I and type III collagens were expressed in the mesangial and the ballooning area of the glomerulus at day seven. Electron microscopy revealed that immature MC and EC forming small capillary lumina appeared in the enlarged mesangial area at day seven. In accordance with the increase of capillaries and the enlargement of the lumina, the number of MC and the amount of mesangial matrix decreased gradually, and most of the glomeruli returned to a normal structure by week 4. These data show that type I and type III collagen produced by transformed MC may be of benefit to proliferation of EC and remodeling of the capillary in Thy-1-induced nephritis.

Animals↗

PubMed2001

Double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver.

A very rare case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver in a 65-year-old-man is discussed. The patient was hospitalized with epigastralgia in May 1997. Abdominal computed axial tomography revealed a tumor located in the left lobe of the liver and a left hepatic lobectomy was performed. The tumor recurred several months after surgery and the patient died on 4 June 1999. At autopsy, both a major tumor mass with extensive involvement, located in the surgical margin, and a small mass located in S7 were discovered. Microscopically, the major tumor was diagnosed as adenosquamous carcinoma and the small one in S7 as hepatocellular carcinoma. To our knowledge, this is the first case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver. The pathological findings support the hypothesis that this tumor developed as a squamous transformation of adenocarcinoma.

Aged↗

PubMed2001

Levels of self-awareness after acute brain injury: how patients' and rehabilitation specialists' perceptions compare.

OBJECTIVE: To examine self-awareness regarding performance on 4 daily living tasks and to test theoretical predictions for a model of self-awareness in persons with acquired brain injury. DESIGN: A comparative design examining the level of self-awareness recorded by patients and actual patient performance as judged by rehabilitation clinicians. SETTING: A community-based residential center providing comprehensive rehabilitation services to persons with acquired brain injury. PARTICIPANTS: Fifty-five persons with acquired brain injury and the identified potential to return to independent function in the community. Ten subjects without brain injury provided comparison data. INTERVENTION: Information was collected by using patient self-report, clinician rating of patient performance, patient rating of non-brain-injured subjects, and clinician rating of non-brain-injured subjects. MAIN OUTCOME MEASURES: Three self-awareness criteria were examined: intellectual, emergent, and anticipatory. Self-awareness was rated for 3 tasks: dressing, meal planning, and money management. RESULTS: Statistically significant differences (p <.05) were found for all levels of self-awareness across the 3 tasks. Persons with brain injury judged their abilities higher than clinician ratings of actual performance. No statistical support was found for a hierarchy among intellectual, emergent, and anticipatory self-awareness. CONCLUSIONS: No evidence was found supporting a hierarchy among levels of self-awareness as defined and measured in the present study. New methods for operationally defining intellectual, emergent, and anticipatory self-awareness are necessary to examine the relationship between self-awareness and performance.

Activities of Daily Living↗

PubMed2001

Targeting HER2: recent developments and future directions for breast cancer patients.

Overexpression of the HER2/neu oncogene (also known as c-erbB2) is a frequent molecular event in multiple human cancers, including breast and ovarian cancer. Patients with cancer that overexpress HER2/neu are associated with unfavorable prognosis, shorter relapse time, and low survival rate. Treatments that target HER2/neu expression in cancer cells have been shown to be useful strategies to significantly reverse the malignancy induced by HER2/neu overexpression. The humanized anti-HER2/neu antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) has proven to be effective in clinical trials in patients with metastatic breast cancer. In addition, tyrosine kinase inhibitors such as emodin can also target the HER2/neu oncogenic activity. Emodin treatment inhibits HER2/neu tyrosine kinase activity and preferentially suppresses the transformation of HER2/neu-overexpressing breast cancer cells. Emodin also sensitizes HER2/neu-overexpressing cancer cells to chemotherapeutic agents, including cisplatin, doxorubicin, etoposide, and paclitaxel. Alternatively, HER2/neu overexpression can be repressed by attenuating the promoter activity of the HER2/neu gene. We have identified a number of potent transcriptional regulators, including the ets family member PEA3 and the adenovirus type 5 E1A, which are able to repress HER2/neu gene expression. Expression of these transcriptional regulators resulted in downregulation of HER2/neu promoter activity and reversed the transformed phenotype of the cancer cells in vitro. In vivo studies show that these HER2/neu repressors can act therapeutically as tumor suppressor genes for tumors that overexpress HER2/neu. These preclinical studies clearly indicate that transcriptional repressors that downregulate HER2/neu can be effective regimens for cancer treatment in a gene therapy format. More importantly, the tumor-free survival rate of treated animals is dramatically increased under nontoxic doses compared with untreated animals. A phase I clinical trial using E1A-liposome in breast and ovarian patients has recently been completed. Following treatment, we observed downregulation of the HER2/neu protein accompanied by E1A expression in both cancer and noncancer cells. Numbers of tumor cells in the pleural effusion or ascites were found to be dramatically reduced after treatment. Furthermore, apoptosis was strongly induced in the tumor cells. A phase II study has been started to further evaluate therapeutic efficacy and tumor suppression mechanisms of E1A. These studies show the clinical potential of targeting HER2/neu in cancer therapy.

Adenovirus E1A Proteins↗

PubMed2001

Fine structure of the skin cells of a stenohaline freshwater fish Cyprinus carpio exposed to diluted seawater.

Seawater diluted to half (1.750% salinity) is lethal for adult carps after 3 h and 15 min. At lower salinities (0.350%-0.875%), the fish survived for longer periods, but only 0.175% salinity was innocuous. In carps, adapted to 0.175% salinity, the secretory activity of pavement cells was very high and their external ridges flattened or even disappeared. Mucus secretion was conspicuous, characterized by holocriny of old cells and apparition of young ones in large numbers. The intracellular mucus droplets often coalesced. Pavement cells and mucus cells were disconnected from their neighboring tissue fabric and were sloughing off. Mitotic figures of filament cells were frequent, suggesting high turnover. Club cells appeared near the epidermal surface. The number of pinocytotic vesicles of the basal cell layer markedly decreased, indicating a possible decrease in dermis-epidermis molecular transfers. Leucocytes, mainly lymphocytes penetrated into the epidermis, where also rodlet cells appeared. The low salinity tolerance of the carp might be related among other possible factors to the absence of chloride cells in the skin.

Age Factors↗

PubMed2001

The inhibitory effects of ginsenosides on protein tyrosine kinase activated by hypoxia/reoxygenation in cultured human umbilical vein endothelial cells.

27 individual ginsenosides and aglycones, together with five extracts from ginseng roots, ginseng leaves, American ginseng roots, American ginseng leaves and non-saponin fraction from roots of Panax ginseng, were tested for their effects on protein tyrosine kinase (PTK) activation induced by an in vitro hypoxia/reoxygenation (H/R) model in cultured human umbilical vein endothelial cells (HUVEC). The results indicated that ginsenoside-Rb1 (3), -Rd (7), -Ra1 (1) and -Ro (27) showed significant inhibitory effects on PTK activation induced by H/R. Dose-response experiments revealed that ginsenoside-Rb1 was the most active compound and it completely blocked PTK activation at a wide range of concentrations. Most protopanaxadiol-type ginsenosides and some protopanaxatriol-type saponins also showed significant effects on PTK activation. However, the crude extracts did not protect against H/R-induced PTK activation.

Cell Hypoxia↗

PubMed2001

Effects of ginsenosides from Panax ginseng on cell-to-cell communication function mediated by gap junctions.

Gap junctions have been shown or are believed to be involved in the pathogenesis of many inherited and acquired human diseases. Agents that regulate the gap junction-mediated intercellular communication (GJIC) function may facilitate prevention and treatment of GJIC-involved diseases. In the present study we examined the effects of 27 ginsenosides isolated from Panax ginseng on GJIC. The results show that compounds 1 (oleanolic acid), 2 (ginsenoside-R0), 3 (ginsenoside-Rb1), 5 (ginsenoside-Rb2), 7 (ginsenoside-Rd), 8 (ginsenoside-Rg3), 12 (panaxadial), 13 (notoginsenoside-R4), 17 [ginsenoside-Rg2 (20S)], 18 (ginsenoside-Rf), and 26 (ginsenoside-F3) did not obviously affect GJIC, whereas compounds 4 (ginsenoside-Rc), 6 (ginsenoside-Rb3), 9 (ginsenoside-Rd2), 10 (notoginsenoside-Fe), 11 (ginsenoside-Rh2),14 (ginsenoside-Ra1), 15 (ginsenoside-Re), 16 [ginsenoside-Rg2 (20R)], 19 (ginsenoside-Ia), 20 [ginsenoside-Rh1 (20S)], 21 [ginsenoside-Rh1 (20R)], 22 (ginsenoside-F1), 23 (protopanaxatriol), 24 (panaxatriol), 25 (ginsenoside-Rg1), and 27 (chikusetsaponin-L8) induced GJIC reductions at various degrees. Compounds 2, 7, and 8 protected against the tyrosine phosphatase inhibitor vanadate-induced GJIC reduction, while compounds 1, 5, 7, and 17 inhibited the cytokine interleukin 1 alpha (IL-1alpha)-induced reduction in GJIC. Nevertheless, no compounds protected against the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced GJIC inhibition. On the other hand, GJIC reductions induced by compounds 6, 9,10, 20, 21, 22, 24, and 25 were inhibited by the tyrosine kinase (TK) inhibitor genistein, while GJIC reductions induced by compounds 6, 9, 14, 16, 19, 21, and 24 were attenuated in the presence of the PKC inhibitor calphostin C. However, GJIC reductions induced by compounds 4, 23, and 27 were not inhibited either by genistein or by calphostin C. These data indicate that various mechanisms are responsible for effects of ginsenosides on GJIC.

Cell Communication↗

PubMed2001

Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model.

BACKGROUND: Peanut allergy is a major cause of fatal and near-fatal anaphylactic reactions to foods. There is no curative therapy for this condition. Traditional Chinese medicines have been reported to have antiallergic properties, which might be useful for treating peanut allergy. OBJECTIVE: The purpose of this study was to investigate the effects of a Chinese herbal formula, FAHF-1, on peanut anaphylactic reactions in a mouse model of peanut allergy. METHODS: Mice were sensitized with freshly ground whole peanut in the presence of cholera toxin and boosted 1 and 3 weeks later. FAHF-1 treatment was initiated 1 week later and continued for 7 weeks. After treatment, mice were challenged with peanut, and anaphylactic symptoms, body temperatures, and plasma histamine and IgE levels were measured. T-cell proliferative responses and cytokine production were also determined. RESULTS: FAHF-1 completely blocked peanut-induced anaphylactic symptoms and markedly reduced mast cell degranulation and histamine release. Peanut-specific serum IgE levels were significantly reduced by 2 weeks of treatment at the time of challenge, and they remained lower 4 weeks after discontinuation of treatment. FAHF-1 significantly reduced peanut-induced lymphocyte proliferation as well as IL-4, IL-5, and IL-13 synthesis but not IFN-gamma synthesis. No toxic effects on liver or kidney functions were observed, nor was there any overall immune suppression. CONCLUSION: FAHF-1 protected peanut-sensitized mice from anaphylactic reactions and significantly reversed established IgE-mediated peanut allergy. This suggests that FAHF-1 might prove valuable for the treatment of peanut allergy.

Administration, Oral↗

PubMed2001

Role of hypothalamic monoamines in nicotine-induced anorexia in menopausal rats.

BACKGROUND: Nicotine reduces body weight by reducing appetite. Estradiol modulates food intake. Menopause or ovariectomy (Ovx) increases food intake and body weight. Nicotine and estradiol individually influence hypothalamic dopamine (DA) and serotonin (5-HT), whose interaction influences food intake and body weight. We investigated whether lower weight gain in menopausal smokers is mediated via changes in hypothalamic DA/5-HT. METHODS: Ovx or sham-operated female rats had 2 microdialysis guide cannulas simultaneously implanted in ipsilateral ventromedial nucleus of hypothalamus (VMN) and contralateral lateral hypothalamic area (LHA). Rats were divided into 4 groups and received a continuous subcutaneous infusion of nicotine or saline Ovx and sham. DA and 5-HT in LHA and VMN were measured by in vivo microdialysis. RESULTS: Nicotine infusion decreased food intake and body weight in Ovx and sham groups. Increase in LHA-DA and VMN-5-HT in sham group occurred with nicotine, whereas an increase in VMN-DA in Ovx groups with and without nicotine and VMN-5-HT in Ovx group with nicotine was observed. CONCLUSIONS: In the presence of estradiol (ovary intact sham-operated rats), nicotine lowers food intake and body weight via increased LHA-DA and VMN-5-HT. In menopause (Ovx rats), nicotine lowers food intake and body weight only via increased VMN-DA and 5-HT. Data show that lower weight gain is mediated via changes in hypothalamic monoamines, primarily via ventromedial hypothalamus.

Animals↗

PubMed2001

Helicobacter pylori infection in rural China: exposure to domestic animals during childhood and adulthood.

Little is known about the mode of transmission of Helicobacter pylori, one of the most common human bacterial infections. Some domestic animals, including the cat, have been suggested as a reservoir of H. pylori disease, but the data have been inconsistent. This paper evaluates the role of exposure to pets and other domestic animals in the etiology of H. pylori in a rural area of China with a high prevalence of H. pylori infection. In this double-blind, population-based, cross-sectional investigation, interviews were completed with 3,288 (1994 seropositive, 1,019 seronegative, 275 indeterminate) H. pylori-infected adults enrolled in a randomized intervention trial in Linqu County, Shandong Province, China. We found no evidence to suggest that exposure to pets or other domestic animals during either childhood or adulthood was related to the prevalence of H. pylori infection. In fact, odds ratios (ORs) were reduced for subjects who had kept a cat (OR = 0.7, 95% CI = 0.4-1.0) or any animal (OR = 0.5, 95% CI = 0.3-0.9) in the house as an adult, or a cat as a child (OR = 0.7, 95% CI =0.5-1.0). ORs were also reduced for all 11 types of animal studied that subjects had kept in their courtyard as an adult. These findings suggest that zoonotic transmission, including that from domestic cats, is an unlikely route of H. pylori infection in this rural Chinese population.

Adult↗

PubMed2001

Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide.

1. To determine which CYP isoenzyme is involved in the N-dealkylation of disopyramide (DP) metabolism in human and dog, and to determine the stereoselectivity of DP metabolism with human CYP and dog CYP isoenzymes, the following in vitro metabolism studies of DP were conducted: correlation between human CYP isoenzyme activities and DP metabolism with human liver microsomes; inhibition of DP metabolism in human and dog liver microsomes with chemical inhibitors of CYP isoenzymes; inhibition of DP metabolism in human microsomes with human CYP antibodies; inhibition of DP metabolism in dog liver microsomes with human and dog CYP antibodies; metabolism of DP with human (CYP3A4) and dog (CYP3A12) cDNA-expressed isoenzymes; determination of Km and Vmax of DP enantiomers by using cDNA-expressed CYP3A4 and CYP3A12. 2. In human liver microsomes, the formation of the mono-N-dealkylated disopyramide (MNDP) metabolite was best correlated with CYP3A4 activities. DP metabolism was substantially inhibited by ketoconazole, troleandomycin (TA) and human CYP3A4 antibody. DP was metabolized by cDNA-expressed CYP3A isoenzymes. In dog liver microsomes, DP metabolism was inhibited by ketoconazole, TA and dog anti-CYP3A12. DP was also metabolized by cDNA-expressed CYP3A12. 3. CYP3A4 and CYP3A12 are the principal isoenzymes involved in DP metabolism in human and dog respectively. There was no stereoselectivity in N-dealkylation of DP by human CYP3A4. However, there was notable stereoselectivity in the N-dealkylation by dog CYP3A12.

Amino Acid Sequence↗

PubMed2001

Plasma progesterone, dehydroepiandrosterone sulfate and estriol levels during labor induction with a sustained-release prostaglandin E2 vaginal insert.

OBJECTIVE: To measure plasma progesterone, dehydroepiandrosterone sulfate (DHEAS) and estriol levels in women induced for labor with a sustained-release vaginal polymer prostaglandin E2 insert, and to analyze the relationships between the changes in hormone levels and Bishop score. METHODS: Twelve primipara and 12 multipara were treated with a sustained-release polymer vaginal prostaglandin E2 insert (0.3 mg/h) for up to 24 h. The Bishop score was assessed at the start and end of therapy, and serum samples were collected at 4-h intervals. Plasma levels of progesterone, DHEAS and estriol were measured by specific radioimmunoassays. RESULTS: Exposure averaged 13.5 +/- 7.2 h. Progesterone levels decreased in the majority of patients (79.2%) after the start of therapy. Higher baseline DHEAS and estriol levels were observed among women who achieved an improvement in Bishop score of at least 4 during prostaglandin E2 treatment. CONCLUSIONS: Higher DHEAS and estriol levels prior to labor induction with prostaglandin E2 may be indicators of a favorable labor outcome. Additional studies are needed to substantiate the decrease in progesterone levels observed in this study and the importance of this phenomenon for the mechanism of labor induction with prostaglandin E2.

Administration, Intravaginal↗

PubMed2001

Spinal nicotinic receptor activity in a genetic model of hypertension.

Intrathecal cytisine, a nicotinic receptor agonist, elicits greater dose-dependent increases in blood pressure, heart rate and nociceptive responses in SHR than normotensive rat strains. Similar to adult rats, cardiovascular and nociceptive responses were augmented in prehypertensive SHR than age-matched WKY. While hydralazine or captopril pretreatment significantly lowered blood pressure in both SHR and WKY rats, responses to i.t. cytisine were still greater in SHR. By contrast, i.t. cytisine elicited responses were not exaggerated in DOCA-salt hypertensive WKY rats. Pressor and irritation responses to i.t. cytisine can be divided into a transient, initial and persisting, late phases. Both are augmented in SHR. In F1 rats, only the late phase pressor and pain responses to i.t. cytisine are similar in magnitude to those observed in SHR suggesting a possible dominant trait in the SHR. Overall, our findings suggest that hyper-responsiveness in nociception and pressor activity to spinal cytisine in SHR may be pathogenetically associated, but not a consequence, of hypertension.

Alkaloids↗

PubMed2001

Comparison of brain responses between frontal and lateral impacts by finite element modeling.

This study was conducted to investigate differences in brain response due to frontal and lateral impacts based on a partially validated three-dimensional finite element model with all essential anatomical features of a human head. Identical impact and boundary conditions were used for both the frontal and lateral impact simulations. Intracranial pressure and localized shear stress distributions predicted from these impacts were analyzed. The model predicted higher positive pressures accompanied by a relatively large localized skull deformation at the impact site from a lateral impact when compared to a frontal impact. Lateral impact also induced higher localized shear stress in the core regions of the brain. Preliminary results of the simulation suggest that skull deformation and internal partitions may be responsible for the directional sensitivity of the head in terms of intracranial pressure and shear stress response. In previous experimental studies using subhuman primates, it was found that a lateral impact was more injurious than a frontal impact. In this study, shear stress in the brain predicted by the model was much higher in a lateral impact in comparison with a frontal impact of the same severity. If shear deformation is considered as an injury indicator for diffuse brain injuries, a higher shear stress due to a lateral impact indicate that the head would tend to have a decreased tolerance to shear deformation in lateral impact. More research is needed to further quantify the effect of the skull deformation and dural partitions on brain injury due to impacts from a variety of directions and at different locations.

Biomechanical Phenomena↗