The significant role of ATG5 in the maintenance of normal functions of Mc3T3-E1 osteoblast.

OBJECTIVE: To observe the effects of autophagy-related gene 5 (ATG5) on the proliferation, differentiation, and apoptosis of Mc3T3-E1 osteoblast as well as the effects of ATG5 on apoptosis of osteoblasts under the conditions of non-oxidative stress and oxidative stress. MATERIALS AND METHODS: ATG5 overexpressing and silencing cell lines were established in this experiment with lentiviral vector and transcription activator-like effect or nuclease (Talen) technique, respectively, using Mc3T3-E1 cells. Cell counting kit-8 (CCK-8) was used to detect the proliferation rate of osteoblasts, and flow cytometry was applied to detect the impacts of overexpressed and silenced ATG5 on the cell cycle. Alizarin red staining was used to detect the mineralization capacity of osteoblasts after 4-week osteoinduction differentiation. Quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot methods were adopted to detect the levels of gene and protein expressions of runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and collagen I (COL-I) correlated with osteoblast differentiation after 48 h of osteoinduction differentiation. The staining with Annexin V-phycoerythrin/7-amino-actinomycin D (Annexin V-PE/7AAD) and flow cytometry were performed to detect the influence of ATG5 on osteoblast apoptosis. RESULTS: Stable ATG5 overexpressing and silencing Mc3T3-E1 cell lines were established successfully. CCK-8 test results showed that ATG5 silence inhibited cell proliferation, but the overexpression of ATG5 did not result in an obvious change in cell proliferation. Cell cycle did not change when ATG5 was overexpressed, while was stagnated in S-phase when silenced. The number of mineralized nodules of cells was reduced notably when ATG5 was silenced, while the overexpression of ATG5 did not have an impact on mineralization capacity of the cell after 4-week of osteoinduction differentiation. The test results of qRT-PCR and Western blotting suggested that ATG5 silence inhibited the gene and protein expressions of Runx2, OCN, and COL-I, while the influence of overexpressed ATG5 on the expressions of genes related to osteoblastic differentiation was not obvious after 48 h of osteoinduction differentiation. ATG5 silence made the cells easier to be damaged by hydrogen peroxide, which resulted in the rise of apoptosis rate of osteoblasts, while the overexpressed ATG5 inhibited osteoblast apoptosis after treatment with hydrogen peroxide for 12 h. CONCLUSIONS: ATG5 silence can lead to inhibition of osteoblast proliferation and differentiation. Moreover, it makes the cells easier to be damaged by oxidative stress, and it causes an increase in apoptosis. However, the overexpression of ATG5 strengthens the anti-oxidative capacity of osteoblasts and reduces apoptosis. ATG5 may be an effective target of anti-oxidative therapy for osteoporosis, which brings a new direction for the treatment of osteoporosis.

Early treatment of SIV+ macaques with an α4ß7 mAb alters virus distribution and preserves CD4+ T cells in later stages of infection.

Integrin α4ß7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4ß7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4ß7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes. These sites are not directly linked to α4ß7 mediated homing; however, the most pronounced reduction in viral load was observed in the colon. Despite this reduction, α4ß7 mAb treatment did not prevent an apparent depletion of CD4+ T cells in gut in the acute phase of infection that is characteristic of HIV/SIV infection. However, α4ß7 mAb appeared to facilitate the preservation or restoration of CD4+ T cells in gut tissues at later stages of infection. Since damage to the gut is believed to play a central role in HIV pathogenesis, these results support further evaluation of α4ß7 antagonists in the study and treatment of HIV disease.

Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies.

COL1A1 gene -1997G/T polymorphism and risk of osteoporosis in postmenopausal women: a meta-analysis.

Studies investigating the association between the COL1A1 gene -1997G/T polymorphism and the risk of osteoporosis in postmenopausal women have reported conflicting results. We performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. We conducted searches of the published literature in the PubMed and Embase databases up to September 2014. We estimated the pooled odds ratios with their 95% confidence intervals to assess the associations using fixed- or random-effect models. Publication bias was investigated by Begg's funnel plot. Meta-analysis was performed using the STATA package version 12.0. No significant association was found between the -1997G/T polymorphism in the COL1A1 gene and osteoporosis risk in the total population analysis (TT vs GG: OR = 1.28, 95%CI = 0.76-2.17; TT vs GT: OR = 1.04, 95%CI = 0.60-1.78; dominant model: OR = 0.84, 95%CI = 0.50-1.40; recessive model: OR = 1.18, 95%CI = 0.84- 1.66). In a subgroup analysis by nationality, the results also showed that no significant associations between the COL1A1 gene -1997G/T polymorphism and osteoporosis risk existed in either Caucasian or Asian populations. No evidence of publication bias was found. In conclusion, the COL1A1 gene -1997G/T polymorphism might not be a risk factor for osteoporosis in postmenopausal women. Further large and well-designed studies are needed to confirm these conclusions.

Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.

Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.

Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection.

De novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Previously, we demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus and alefacept (AMR regimen) reliably induced early DSA production with AMR in a nonhuman primate kidney transplant model. Five animals were assigned as positive AMR controls, four received additional belatacept and four received additional anti-CD40 mAb (2C10R4). Notably, production of early de novo DSA was completely attenuated with additional belatacept or 2C10R4 treatment. In accordance with this, while positive controls experienced a decrease in peripheral IgM(+) B cells, bela- and 2C10R4-added groups maintained a predominant population of IgM(+) B cells, potentially indicating decreased isotype switching. Central memory T cells (CD4(+) CD28(+) CD95(+)) as well as PD-1(hi) CD4(+) T cells were decreased in both bela-added and 2C10R4-added groups. In analyzing germinal center (GC) reactions in situ, lymph nodes further revealed a reduction of B cell clonal expansion, GC-follicular helper T (Tfh) cells, and IL-21 production inside GCs with additional belatacept or 2C10R4 treatment. Here we provide evidence that belatacept and 2C10R4 selectively suppresses the humoral response via regulating Tfh cells and prevents AMR in this nonhuman primate model.

A study on knowledge and attitude toward brain death and organ retrieval among health care professionals in Korea.

PURPOSE: The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval. METHODS: Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA). RESULTS: There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001). CONCLUSION: Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals.

Postoperative pain and influencing factors among living liver donors.

PURPOSE: In Korea, living donor transplantation is increasing steadily as a life-saving alternative. It is essential to provide living donors the mental and physical care they need throughout their lives including postoperative period. Therefore, this study explored postoperative pain among living liver donors. METHODS: We used a convenience sampling at a university-affiliated hospital from March 1 to August 30, 2009 including 102 subjects. Face-to-face interviews with questionnaires and medical records were used to assess postoperative pain levels, state and trait anxiety as well as satisfaction. Data were analyzed using SPSS 14.0 (SPSS Inc., Chicago, Ill, USA). RESULTS: Average age of donors was 28.9±7.7 years (ranged 16 to 53) with 70.6% male. Most donors (80.4%, n=82) were immediate family members. Ninety-one (89.2%) participants made the decision by themselves. To control postoperative pain, all participants had patient-controlled anesthesia with several types of analgesics as prescribed by physician's preference. The mean values of state anxiety, trait anxiety, and satisfaction in this study were 2.1±1.89, 36.7±7.25 and, 8.9±1.79, respectively. Multivariate analysis showed that trait anxiety and number of analgesics use were significantly associated with postoperative pain. Overall, approximately 29.7% of total variability in postoperative pain could be explained by the nine variables in this model (R2=0.297, F9,102=4.28, (P<.001). There was no multicollinearity checked by tolerance, variation inflation factor, or condition index. CONCLUSION: This study of postoperative pain among living liver donors may contribute to developing the safest, most effective strategy to relieve postoperative pain after living liver donation.

Safety of ultra-rapid intravenous infusion of hepatitis B immunoglobulin in liver transplant recipients.

PURPOSE: To evaluate the safety of institutional protocol for ultra-rapid hepatitis B immunoglobulin (HBIG) infusion (10,000 IU in 30 minutes) for hepatitis B virus prophylaxis in adult liver transplant recipients. METHODS: In this case-controlled study, prospectively recruited liver transplant recipients received ultra-rapid infusions of HBIG (10,000 units in 30 minutes) for 6 months. The historical control group consisted of patients who had received 1-hour HBIG infusions (conventional rapid infusion) for the precedent 6 months. RESULTS: We found that 1472 patients had received 5744 ultra-rapid HBIG infusions, whereas 1343 patients had received 5200 conventional rapid HBIG infusions. Adverse side-effects were observed after 7 (0.13%) and 9 (0.16%) infusions, respectively (P = .763). The number of infusions per month increased significantly, from 878 ± 34 before the introduction of ultra-rapid infusion to 957 ± 29 afterwards (P < .001), an increase of 10.5%. The maximal capacity of HBIG infusions per day in the outpatient clinic increased from 53 for conventional rapid infusion to 65 for ultra-rapid infusion, without expansion of the outpatient facility or equipment. CONCLUSIONS: Nearly all adult liver recipients able to tolerate 1-hour infusions of HBIG can also tolerate ultra-rapid infusions well. Thus, it seems to be reasonable to perform ultra-rapid infusion protocol widely for patient convenience.

Decision-related factors and attitudes toward donation in living related liver transplantation: ten-year experience.

INTRODUCTION: Living related liver transplantation (LRLT) has been performed since 1994 in Korea; more than 600 donors have contributed to our successful LRLT program for 10 years. Although the decision to donate is difficult and the donors need a formal psychosocial assessment, no system has been available to us for the assessment. This survey was performed as a presurveillance for the development of a psychosocial assessment protocol. METHODS: A survey questionnaire included 31 questions on general and medical characteristics, factors, and processes related to the decision for donation. Donors of partial livers at least 6 months ago during the period from December 1994 to August 2003 and whose address could be confirmed by telephone were enrolled in the study. RESULTS: A questionnaire was sent by mail to 441 contactable donors of whom 209 (47.4%) responded. Male-to-female ratio was 2:1 and mean age was 32.8 years (range: 16 to 60 years). The number of spousal donors was 120 (57.4%) and 164 (78.5%) donors were employed at the time of donation. Protestants, Buddhists, and Catholics were 29.2%, 19.1%, and 14.8%, respectively. Parents were the most common recipients (33.0%), followed by siblings (17.2%), extended family members (17.2%), and children (15.8%); one hundred eighty nine (90.4%) donors had decided by themselves, the major reason for donation in 192 (91.9%) donors was "to save the lives of family members and relatives." The first person who suggested donation was the donor (64.1%), followed by family members (23.9%) or the attending physicians (8.6%). Although 70.8% of donors answered that they were not hesitant to donate at the time of decision, 44.5% were uneasy at the possibility of being unable to sustain a normal life after donation, at their lack of knowledge on organ donation, and about the pain and fear of surgery. Family members and relatives (53.3%), medical personnel (46.7%), and previous donors (35.4%) were the preferable counselors compared to transplantation institutions and clergymen. The large majority (80.8%) of donors would encourage others to donate. CONCLUSIONS: Although the decision to donate was made by the donors themselves in most cases and they appeared firm and determined about their decision, a significant number of donors felt uneasy about possible complications of organ donation and effects on their lives after donation. A precise and formal psychosocial assessment protocol is needed to support and secure their decision before and after donation.

Nucleotide sequences of genome segments S6, S7 and S10 of Dendrolimus punctatus cypovirus 1.

The nucleotide sequences of genome segments S6, S7 and S10 of Dendrolimus punctatus cypovirus 1 Hunan I (DpCPV-HN(I)) and DpCPV-HN(I)-Se(3) (DpCPV-HN(I) passed three times in Spodoptera exigua) were determined. Segment S10 was 944 nucleotides in length and encoded a polyhedrin of 248 amino acids (28,439 Da). Only two nucleotide mutations were found between DpCPV-HN(I) S10 and DpCPV-HN(I)-Se3 S10, and the deduced amino acid sequences of the polyhedrin proteins were identical. Segment S7, 1 501 nucleotides, encoded a protein of 448 amino acids ( approximately 50 kDa; p50). Thirty-one nucleotide mutations were found between DpCPV-HN(I) S7 and DpCPV-HN(I)-Se3 S7, but these resulted in only four amino acid changes. DpCPV-HN(I) S6 encoded a protein of 561 amino acids (63,688 Da; p64). The amino acid sequence of p64, had a high leucine content (10%), and contained a leucine zipper motif and one ATP/GTP-binding site motif.

Experimental infection of mice with tightly coiled spiral bacteria ("Candidatus Helicobacter suis") originating from the pig stomach.

Mice (n=34) were inoculated orally with a gastric homogenate from a pig infected with tightly coiled spiral bacteria (TCSB). In mice killed in pairs at 16 intervals up to 108 weeks post-inoculation (pi), TCSB were invariably found, mainly in the mucosal surface, gastric pits, intercellular spaces, cytoplasm of surface epithelial cells, and lumina of gastric glands. Histopathologically, infiltration of lymphocytes and plasma cells was seen from 8 weeks pi onwards, gradually increasing as infection progressed. From 64 weeks pi onwards, the formation of large follicles was observed in the lamina propria and submucosa, together with severe necrosis of surface epithelial cells. Glandular epithelial cells in the fundic mucosa were markedly dysplastic and intruded through the basement membrane into the submucosal layer. Common antigenicity between TCSB and Helicobacter pylori was demonstrated by Western blotting, ELISA, and immunohistochemistry. The sequence of the 16S rDNA fragment of 374 bp showed 100% homology with the 16S rRNA gene of "Candidatus Helicobacter suis". Experimental infection of the gastric mucosa of mice with TCSB was closely associated with chronic gastritis and dysplastic lesions.

Molecular characterization of segments 7-10 of Dendrolimus punctatus cytoplasmic polyhedrosis virus provides the complete genome.

The nucleotide sequences of genomic segments S7-S10 from Dendrolimus punctatus cypovirus strain Hunan (DpCPV-Hn) have been determined. This provides the complete genome sequences of DpCPV-Hn. Each segment of S7-S10 possess a single segment each. Homology searches showed that the nucleotide sequences and the deduced amino acid sequences of DpCPV S7-10 had high level of identities with those of Bombyx mori cypovirus (BmCPV) S7-10, respectively. While the amino acid sequences of the proteins encoded by DpCPV S7 and S8 have low identities with those of the proteins encoded by type 14 Lymantria dispar cypovirus S7 and S8, respectively. DpCPV S7 encodes viral structural protein VP5, S8 and S9 encode viral non-structural proteins, and S10 encodes polyhedrin gene, according to the function of the genome segments of BmCPV. There are glutamic-acid-rich and proline-rich domains in the central region of DpCPV S8 encoded protein. A nuclear localization signal was found in the protein encoded by DpCPV S9. Phylogenetic analysis of RNA-dependent RNA polymerases from nine viruses of the family Reoviridae and polyhedrin from eight viruses of the genus Cypovirus indicate that DpCPV is a type 1 cypovirus, more closely related to BmCPV than to other cypovirus species. These results also support the classification of CPV groups based on the electrophoretic migration of genomic dsRNA.

Genomic sequence analyses of segments 1 to 6 of Dendrolimus punctatus cytoplasmic polyhedrosis virus.

The complete nucleotide sequences of genomic segments S1 to S6 from Dendrolimus punctatus cypovirus 1 (DpCPV-1) have been determined. Each segment of S1 to S6 possess a single open reading frame. Conserved motifs 5' (AGUAA) and 3'(GUUAGCC) were found at the ends of each segment. Comparison of the proteins of DpCPV with those of other members in the family Reoviridae lead us to suggest that S1, S3, S4 and S6 encode the viral structural protein VP1, VP2, VP3 and VP4, respectively. S5 encoded viral non-structural protein p100 and S2 encodes an RNA-dependent RNA polymerase (RdRp). Motif analysis shows that VP3 is similar to the methyltransferase of Methanosarcina mazei Goe1, VP4 has motifs for leucine zipper and ATP/GTP-binding sites, and p100 is remarkably similar to foot-and-mouth disease virus 2A protease (FMDV 2Apro). Phylogenetic analysis of RdRps from nine viruses of the family Reoviridae indicates that DpCPV is a type 1 cypovirus, more related to Bombyx mori cypovirus (BmCPV) than to other cypovirus species. DpCPV is more related to Rice ragged stunt virus (RRSV) than to other members of different genera of the family Reoviridae, which seems to confirm the previous hypothesis that plant reoviruses originated from insect reoviruses.

Prospective study of the incidence and outcome of intra-abdominal hypertension and the abdominal compartment syndrome.

BACKGROUND: Intra-abdominal hypertension has been recognized as a source of morbidity and mortality in the traumatized patient following laparotomy. Multiple organ dysfunction attributable to intra-abdominal hypertension has been called the abdominal compartment syndrome. The epidemiology and characteristics of these processes remain poorly defined. METHODS: Intra-abdominal pressure was measured prospectively in all patients admitted to a trauma intensive care unit over 9 months. Data were gathered on all patients with intra-abdominal hypertension. RESULTS: Some 706 patients were evaluated. Fifteen (2 per cent) of 706 patients had intra-abdominal hypertension. Six of the 15 patients with intra-abdominal hypertension had abdominal compartment syndrome. Half of the patients with abdominal compartment syndrome died, as did two of the remaining nine patients with intra-abdominal hypertension. Patients with abdominal compartment syndrome had a mean intra-abdominal pressure of 42 mmHg compared with 26 mmHg in patients with intra-abdominal hypertension only (P < 0.05). CONCLUSION: The incidence of intra-abdominal hypertension and abdominal compartment syndrome was 2 and 1 per cent respectively. Intra-abdominal hypertension did not necessarily lead to abdominal compartment syndrome, and often resolved without clinical sequelae. Abdominal compartment syndrome did not occur in the absence of earlier laparotomy. Abdominal compartment syndrome was associated with a marked increase in intra-abdominal pressure (above 40 mmHg).

Benzodiazepine discontinuation difficulties in panic disorder: conceptual model and outcome for cognitive-behavior therapy.

There is consistent support for the efficacy of cognitive-behavior therapy (CBT) to aid the successful discontinuation of benzodiazepine (BZ) medication in patients with panic disorder, and help these individuals maintain treatment gains while off medication. In this article, we provide a conceptual model for BZ discontinuation difficulties in patients with panic disorder. Outcome studies are reviewed, and are placed in the context of other evidence for the efficacy of CBT in patients with this disorder.

Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression.

Hematein is a compound isolated from Caesalpinia sappan that has been used in oriental medicine as both an analgesic and an anti-inflammatory agent. In this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZW) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n=6), a probucol-supplemented (0.25% in diet) group (n=6), and a control group (n=6). After 8 weeks of treatments, the extent of the atherosclerotic lesions was significantly reduced in the hematein-supplemented group and the probucol-supplemented group without changing plasma lipoprotein levels. Hematein and probucol prevented the up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCAM-1 and of monocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density lipoprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, hematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the present study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibition of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion development in the rabbit.

Therapeutic effect of hyaluronic acid on experimental osteoarthrosis of ovine temporomandibular joint.

A symptomatic relief by hyaluronic acid (HA, MW: 3.5 x 10(6)), which is synthesized by Streptococcus spp, was investigated in experimental ovine osteoarthrosis. Bilateral osteoarthrosis (OA) of the temporo-mandibular joints (TMJs) was induced by perforating discs and by scrapping subchondral condylar surface. HA was intra-articularly injected into the left joints of 6 sheep on 7, 10, 14, 17 and 21 days after the operation and physiological saline as the control was injected into the contralateral (right) joints on the same day. Three sheep were killed at I month post-operation (MPO) and the remaining three sheep were killed at 3 MPO. Various responses such as proliferation of fibrous tissue, denudation, erosion, osteophyte formation, subcortical cyst formation and ankylosis were observed radiographically and histopathologically. The treatment of HA ameliorated the degenerative changes and lowered the osteoarthrotic score in the left joints at I MPO (9.96 vs 5.81) and 3 MPO (10.86 vs 5.29) compared to the right joints. These results indicate that a repeated intra-articular injection of HA inhibits the progression of OA in ovine TMJs by inducing the development of articular cartilage and by reducing the proliferation of fibrotic tissue.

Ketanserin attenuates the behavioural effects of corticosterone: implications for 5-HT(2A) receptor regulation.

The effects of chronic corticosterone treatment on sexual behaviour and wet-dog shakes were investigated in both female and male rats. The serotonergic type 2A (5-HT(2A)) receptor antagonist ketanserin was administered to test the hypothesis that the behavioural effects of corticosterone were mediated by increased 5-HT(2A) receptor activity. Rats were randomly assigned to one of four chronic treatment groups: control, ketanserin alone, corticosterone alone, or ketanserin and corticosterone. Ketanserin attenuated the corticosterone-induced changes in both sexual behaviour and wet-dog shakes. Ketanserin alone had no effect on these behaviours. Results suggest that increased 5-HT(2A) receptor activity mediates the effects of corticosterone on sexual behaviour and wet-dog shakes.