黄芩苷对牙龈成纤维细胞和牙周膜细胞pro-MMP-1和MMP-3 表达的影响

目的　检测黄芩苷对白细胞介素 1β(IL 1β)诱导作用下人牙龈成纤维细胞 (HGF)分泌基质金属蛋白酶 1酶原 (pro MMP 1)的量和牙周膜细胞 (PDLCs)基质金属蛋白酶 3(MMP 3)表达的变化。方法　体外培养HGF和PDLCs,分别运用ELISA和免疫组化方法检测 pro MMP 1的量和MMP 3的表达。结果　与对照组的 (1 96 0± 0 176 ) μg/L相比 ,1μg/L的IL 1β能够显著促进HGF分泌 pro MMP 1(3 333± 0 12 3) μg/L ,且增加PDLCsMMP 3的表达 (P <0 0 0 1) ;加入黄芩苷后能降低HGF的pro MMP 1分泌量 ,其作用呈浓度 (10～ 10 0 0 μg/L)依赖性 ;黄芩苷对IL 1β诱导下PDLCs合成MMP 3的能力没有影响 ,但是能够抑制MMP 3的释放。结论　黄芩苷能够抑制由IL 1β介导的HGF分泌pro MMP 1和PDLCMMP 3的表达 ,提示黄芩苷可用于牙周病的防治。     

Cooperative enhancement of F-cell formation in baboons treated with erythropoietin and hydroxyurea

Chronically anemic baboons on a continuous hydroxyurea regimen were treated with pulsed doses of recombinant human erythropoietin (rHuEpo) to test whether the combination of these two compounds, which individually induce F-cell production, can enhance further F-cell output. A low-F-cell-responding animal under chronic hydroxyurea treatment was given three separate pulses of Epo and responded with F- reticulocyte increments that were similar to the sum increments caused by either hydroxyurea alone or rHuEpo alone. The same results were obtained in a high-F-responding animal similarly treated. These findings suggest that rHuEpo and hydroxyurea can increase F cell numbers in an additive fashion. It is speculated that both compounds act through perturbation of erythroid differentiation kinetics.     

Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease

Elevated homocysteine (Hcy) levels are observed in two apparently unrelated diseases: neural-tube defects (NTD) and premature vascular disease. Defective human methionine synthase (MS) could result in elevated Hcy levels. We sequenced the coding region of MS in 8 hyperhomocysteinaemic patients (4 NTD patients and 4 patients with pregnancies complicated by spiral arterial disease, SAD). We identified only one mutation resulting in an amino acid substitution: an A-->G transition at bp 2756, converting an aspartic acid (D919) into a glycine (G). We screened genomic DNA for the presence of this mutation in 56 NTD patients, 69 mothers of children with NTD, 108 SAD patients and 364 controls. There was no increased prevalence of the GG and AG genotypes in NTD patients, their mothers or SAD patients. The D919G mutation does not seem to be a risk factor for NTD or vascular disease. We then examined the mean Hcy levels for each MS genotype. There was no correlation between GG- or AG-genotype and Hcy levels. The D919G mutation is thus a fairly prevalent, and probably benign polymorphism. This study, though limited, provides no evidence for a major involvement of MS in the aetiology of homocysteine-related diseases such as NTD or vascular disease.      

Divalent cation-dependent and independent surface expression of thrombospondin on thrombin-stimulated human platelets

Thrombospondin (TSP), a platelet alpha-granule protein, becomes expressed on the surface of thrombin-stimulated platelets. The surface expression of this protein occurs through two distinct mechanisms. At low platelet concentrations (1 X 10(8)/mL), a divalent ion-dependent, low-capacity mechanism predominates. At higher cell concentrations, a divalent ion-dependent, higher capacity mechanism prevails that can account for greater than 90% of all the TSP surface expression measured. This mechanism requires the presence of both calcium and magnesium (Ca + Mg). The dependence of the divalent ion-dependent surface expression on platelet concentration suggests that release of the molecule from the cell followed by its binding to the cell surface mediates this component of the endogenous TSP-platelet interaction. These data are consistent with a two-receptor model for the platelet- surface expression of the endogenous TSP pool.     

In vitro studies of lactoferrin and murine granulopoiesis

Human lactoferrin (LF) has been reported to inhibit in vitro granulopoiesis by means of decreasing colony-stimulating activity production by monocytes. We performed a series of experiments to determine if the reported experimental results could be replicated using highly purified murine LF and murine target cells. Three different types of experiments were performed. (1) Medium was conditioned by lung, femoral shaft, and adherent peritoneal cells in the presence and absence of LF, and the granulopoietic stimulating activity in the conditioned media was assayed by means of a 7-day agar colony assay and a 3-day liquid slide chamber assay, which quantitates 3H-TdR incorporation into DNA. (2) In cultures stimulated by an underlayer of adherent peritoneal cells, marrow cell colony formation in agar was determined after 7 days of culture in the presence or absence of LF. (3) LF was added to 3-day liquid marrow cell cultures that had been stimulated by lung or femoral shaft conditioned media. In all experimental situations, highly purified, iron-saturated LF in concentrations up to 10(-7) M had no effect on in vitro granulopoiesis. These results do not support LF's reputed regulatory role in granulopoiesis.     

Mortality is influenced by locality in a major HIV/AIDS epidemic

Objectives

The aim of the study was to compare the risks of death among HIV‐infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users.

Methods

We compared the clinical and socioeconomic characteristics of HIV‐infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan–Meier methods were used to estimate the cumulative mortality rates. Results We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV‐experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24].

Conclusions

A threefold increase was observed in the risk of death among HIV‐infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.     

Treatment decision-making for a post-traumatic malocclusion in an elderly patient: A case report.

Traumatic dental injuries in elderly patients are a rising trend due to demographic and social changes of the population. Older dentulous patients in good health have become increasingly common. The development of a post-traumatic malocclusion is a common sequela resulting from mandibular condyle fracture, as in the case reported in this paper. The decision-making process led the authors to rule out conservative treatment options and to perform orthognathic surgery on an 81-year-old patient, an unprecedented report in the literature. At one-year follow-up, prophylactic therapy, a specific surgical technique, and osteotomy fixation have restored the occlusion to the pre-traumatic condition.     

A bleeding disorder due to deficiency of alpha 2-antiplasmin

A deficiency of alpha 2-antiplasmin has been identified in a female patient with severe and frequent bleeding episodes. Routine coagulation and platelet assays of the patient's plasma were within normal limits. However, abnormally rapid whole blood or dilute plasma clot lysis times and an abnormal FXIII test in which clots were lysed in the presence of urea or saline suggested an abnormal fibrinolytic system. Analysis of alpha 2-antiplasmin levels by radioimmunoassay revealed less than 1.0 microgram/ml alpha 2-antiplasmin. Functional assays indicated an alpha 2-antiplasmin level less than or equal to 10% of normal. Addition of purified alpha 2-antiplasmin to the patient's plasma restored its ability to inhibit plasmin in in vitro assays, and mixtures of patient plasma with normal plasma did not interfere with the antiplasmin activity of the normal plasma. Whereas normal platelets contain 68 ng alpha 2-antiplasmin/10(9) platelets, platelets from the patient contained 30% of the normal level of antigen. Analysis of alpha 2- antiplasmin functional and antigenic levels in the plasma of both parents and four siblings of the propositus provided evidence consistent with an autosomal mechanism of inheritance of alpha 2- antiplasmin deficiency. One sibling appeared to be homozygous and three siblings and the parents were heterozygous for the deficiency. Two heterozygotes had positive bleeding histories. The association of a bleeding disorder with a deficiency of alpha 2-antiplasmin emphasizes that lack of regulation of the fibrinolytic system can result in a hemostatic dysfunction.