Endovascular treatment for acute ischaemic stroke caused by isolated internal carotid artery occlusion: treatment strategies, outcomes, and prognostic factors.

AIM: To describe the experience of endovascular treatment (EVT) of acute ischaemic stroke caused by isolated internal carotid artery (ICA) occlusion, with emphasis on treatment strategies, outcomes, and prognostic factors. MATERIALS AND METHODS: A retrospective examination was performed of 66 consecutive patients with acute moderate-to-severe stroke who underwent EVT for isolated ICA occlusion from July 2016 to June 2021. The modified thrombolysis in cerebral ischaemia (mTICI) score was used to evaluate reperfusion outcomes. A multivariate analysis was performed to identify risk factors associated with poor 90-day outcome (modified Rankin Scale [mRS] 3-6). RESULTS: The National Institutes of Health Stroke Scale (NIHSS) median score of the 66 patients at admission was 15. Twelve patients (18.2%) showed thrombus migration to the M1 segment or proximal M2 during EVT and underwent additional intracranial thrombectomy. Successful reperfusion (mTICI 2b-3) was achieved in 60 patients (90.9%) and complete reperfusion (mTICI 3) in 42 (63.6%). A poor functional outcome was seen in 27 patients (40.9%). The rate of 90-day mortality was 9.1% (6/66). Higher NIHSS scores and a lower Alberta Stroke Program Early CT Score (ASPECTS) were independently associated with poor outcomes. Complete reperfusion was the only treatment factor with a significant predictive value (adjusted odds ratio [OR] 0.03; 95% CI = 0.01 to 0.25; p=0.001). CONCLUSION: Endovascular therapy is safe and effective in patients with acute ischaemic stroke due to isolated ICA occlusion. Prevention of thrombus migration and complete reperfusion should be the aim of EVT.

Hypoperfusion intensity ratio correlates with clinical outcome of endovascular thrombectomy in acute ischaemic stroke patients with late therapeutic window.

AIM: To evaluate the prognostic value of the hypoperfusion intensity ratio (HIR) on 90-day clinical outcome in acute ischaemic stroke (AIS) patients with late therapeutic window. MATERIALS AND METHODS: One hundred and sixty-eight consecutive AIS patients with anterior-circulation large-vessel occlusion who underwent endovascular thrombectomy during the late window were enrolled retrospectively. Clinical data, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), and perfusion parameters included ischaemic core, hypoperfusion volume, mismatch volume between core and penumbra, and the HIR were assessed and compared between patients with or without favourable outcomes (defined as modified Rankin Scale score of 0-2). Statistical analysis included binary logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: A favourable outcome was achieved in 76 (45.2%) patients. In univariable analysis, age, National Institutes of Health Stroke Scale (NIHSS) score at admission, ASPECTS score, HIR, ischaemic core, and hypoperfusion volume were significantly associated with functional outcome (p<0.05). In multivariate analyses, age (OR 0.95; 95% CI 0.92-0.99), NIHSS score at admission (OR 0.89, 95% CI 0.84-0.96) and HIR (OR 0.018, 95% CI 0.003-0.113) remained as independent outcome predictors (p<0.01). The optimal threshold of HIR was 0.36 (sensitivity 70.7%, specificity 61.8%). The combination of age, NIHSS score at admission, and HIR yield good performance for outcome prediction with an area under the ROC curve of 0.815 (sensitivity 88.2%, specificity 64.1%), significantly higher than individual variable (p<0.05). CONCLUSION: Low HIR was a predictor for favourable outcome in AIS patients with late therapeutic window. Integrating HIR with clinical variables improved the ability for outcome classification.

Two classic OBPs modulate the responses of female Holotrichia oblita to three major ester host plant volatiles.

Insects possess a fairly sophisticated olfactory system in their antennae to detect odorants essential for their survival and reproduction. Among them, insect first perceives odour sources by odorant-binding proteins (OBPs) to locate host-plants. Methyl salicylate, (Z)-3-hexenyl acetate and dibutyl phthalate are major volatile components of Ulmus pumila and Ricinus communis and elicit strong responses of the scarab beetle Holotrichia oblita adults. However, olfactory perception of the scarab beetle to these odorant compounds is unclear. In the current study, we cloned the OBP6 and OBP7 of H. oblita. The expression pattern shows that the two genes were highly expressed in the antennae of female beetles. Binding assays verified that the HoblOBP6 had a better binding affinity to methyl salicylate, and so did HoblOBP7 to (Z)-3-hexenyl acetate and dibutyl phthalate. The effect on the responses of female beetles to the three compounds was decreased significantly after these two genes were silenced by RNA interference. These results indicate that HoblOBP6 and HoblOBP7 are essential for female H. oblita perception of methyl salicylate, (Z)-3-hexenyl acetate and dibutyl phthalate. Our study provides important insights into the olfactory mechanism of female H. oblita to ester plant volatiles and could facilitate the development of potential pest control strategies in the field.

THE PI3K/Akt/mTOR Signaling Pathway Plays a Role in Regulating Autophagy in Mouse Oocytes During Vitrification-warming and in vitro Maturation.

BACKGROUND: It has been shown that vitrified-warmed oocytes exhibit autophagic activation. However, its regulatory molecular mechanism of autophagy needs to be clarified. OBJECTIVE: To determine the role of signaling pathway of PI3K/Akt/mTOR in the regulation of autophagy in oocytes during vitrification-warming and IVM. MATERIALS AND METHODS: Oocytes from mice were vitrified-warmed and IVM. The expressions of LC3-II, Beclin-1, PI3K, Akt, and mTOR protein were determined. Moreover, the ATP level, viability of vitrified-warmed oocytes, and their developmental potential were measured. RESULTS: At 6 h of incubation of warmed oocytes, the LC3-II and Beclin-1 expressions were markedly up-regulated, whereas PI3K, Akt, and mTOR proteins expressions were significantly down-regulated. In addition, autophagy inhibition significantly decreased ATP level, viability of oocytes, and their developmental potential. CONCLUSION: Autophagy plays a protective role in the oocytes during vitrification-warming and IVM. The PI3K/Akt/mTOR pathway participated in regulating autophagy activity in oocyte during vitrification-warming and IVM.

Lack of Association between SLC6A11 Genetic Polymorphisms and Drug Resistant Epilepsy in Chinese Han Population.

BACKGROUND: Epilepsy is one of the most common chronic neurological diseases. A recent study has implicated that the genetic variants of the SLC6A11 gene encoding GAT-3, an astrocytic GABA transporter, may influence the efficacy of antiepileptic drugs (AEDs) in the Korean population. METHODS: This study aims to investigate the possible associations between SLC6A11 gene and drug resistance in Chinese epilepsy patients. Genomic DNA from 240 drug resistant epilepsy (DRE) patients and 336 drug responsive epilepsy patients was tested for the polymorphisms using Illumina GoldenGate assay. RESULTS: None of the 14 tagSNP alleles and genotypes were found to be related to DRE. The frequencies of haplotype 5 was obviously lower in DRE patients than that in drug responsive epilepsy patients (1% vs. 4%, OR = 2.56 [0.107 - 0.763], p = 0.01). However, after the correction of multiple comparisons with Bonferroni's method, we found that haplotype 5 was not associated with DRE. CONCLUSIONS: Our study suggested no existing association between the 14 SNPs of SLC6A11 and AEDs efficacy in the Chinese Han population.

[Analysis of epidermal growth factor receptor mutations and its clinico-pathologic characteristics of the primary lung adenocarcinoma in Xinjiang Uighur Autonomous Region].

OBJECTIVE: To clarify the relationship between epidermal growth factor receptor (EGFR) mutations and the clinicopathologic features of primary lung adenocarcinomas in Xinjiang. METHODS: The mutations of EGFR gene at exons 18-21 in 59 cases (including 15 cases of Uighur and 44 cases of Han) of lung adenocarcinoma tissues, which were obtained from surgical resection, were detected by amplification refractory mutation system (ARMS) method. And the relationships among mutations, race and clinicopathologic features were analyzed. RESULTS: The frequencies of EGFR mutations in lung adenocarcinoma were 20% for Uighur, which was lower than that in Han (54.5%), P<0.05. The deletion mutations at exon 19 were seen in 2 of 15 Uighur cases and 9 of 44 Han cases. EGFR mutations were present, including exon 21 L858R in one Uighur case and 12 Han cases, exon 18 G719X in two of 44 cases of Han, exon 21 L861Q in one of them. On histological type, the frequencies of EGFR mutation in alveolar predominant adenocarcinoma was 71% (22/31), which was higher than both that in solid predominant and mucinous carcinoma ( 6.7%, 20% respectively). According to statistic analysis, EGFR mutations were without correlation with the patient's gender, age, location, gross type, smoking status and lymph node metastasis(P>0.05). EGFR mutation was more frequent in well-differentiated cancer, mainly in acinar carcinoma, while poorly differentiated adenocarcinoma and mucous adenocarcinoma were lower. CONCLUSION: There was a difference of EGFR mutation in primary lung adenocarcinoma between Uighur and Han in Xinjiang, perhaps reflecting ethnic genetic variation, which is worth further analyzing. EGFR mutation was commonly detected in well or middle differentiated adenocarcinoma, mainly in acinar carcinoma.

[Analysis of epidermal growth factor receptor mutations and its clinico-pathologic characteristics of the primary lung adenocarcinoma in Xinjiang Uighur Autonomous Region].

OBJECTIVE: To clarify the relationship between epidermal growth factor receptor (EGFR) mutations and the clinicopathologic features of primary lung adenocarcinomas in Xinjiang. METHODS: The mutations of EGFR gene at exons 18-21 in 59 cases (including 15 cases of Uighur and 44 cases of Han) of lung adenocarcinoma tissues, which were obtained from surgical resection, were detected by amplification refractory mutation system (ARMS) method. And the relationships among mutations, race and clinicopathologic features were analyzed. RESULTS: The frequencies of EGFR mutations in lung adenocarcinoma were 20% for Uighur, which was lower than that in Han (54.5%), P<0.05. The deletion mutations at exon 19 were seen in 2 of 15 Uighur cases and 9 of 44 Han cases. EGFR mutations were present, including exon 21 L858R in one Uighur case and 12 Han cases, exon 18 G719X in two of 44 cases of Han, exon 21 L861Q in one of them. On histological type, the frequencies of EGFR mutation in alveolar predominant adenocarcinoma was 71% (22/31), which was higher than both that in solid predominant and mucinous carcinoma ( 6.7%, 20% respectively). According to statistic analysis, EGFR mutations were without correlation with the patient's gender, age, location, gross type, smoking status and lymph node metastasis(P>0.05). EGFR mutation was more frequent in well-differentiated cancer, mainly in acinar carcinoma, while poorly differentiated adenocarcinoma and mucous adenocarcinoma were lower. CONCLUSION: There was a difference of EGFR mutation in primary lung adenocarcinoma between Uighur and Han in Xinjiang, perhaps reflecting ethnic genetic variation, which is worth further analyzing. EGFR mutation was commonly detected in well or middle differentiated adenocarcinoma, mainly in acinar carcinoma.

Changes and significance of the fibrinolytic system following two pulmonary thromboembolisms in a rabbit model.

In this study, we examined the changes in the fibrinolytic system in a rabbit model of two acute pulmonary thromboembolisms (PTE). Fourteen healthy adult New Zealand white rabbits were divided into three groups: the single PTE group (five rabbits), the double PTE group (five rabbits), and the control group (four rabbits). A rabbit model of acute pulmonary embolism was established, and immunohistochemistry and polymerase chain reaction (PCR) were performed on tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) in plasma, and pulmonary embolism tissue. Plasma results: 1) t-PA levels: one hour following the initial modeling, the levels of t-PA in the modeling groups were significantly lower than those in the control group (P<0.05). In addition, the t-PA levels in the double PTE group were found to be lower after the modeling, as compared to the pre-modeling period (P<0.05). One hour after the second modeling, the double PTE group had lower t-PA levels compared to the control group (P<0.05). However, t-PA rebounded two hours after modeling in the double PTE group. One week after the second modeling, the double PTE group had higher t-PA levels compared to the other two groups (P<0.05). 2) PAI-1 results: one hour after the initial modeling, PAI-1 levels in the two modeling groups were lower compared to the pre-modeling period and control groups (P<0.05). Two hours following modeling, PAI-1 levels in both modeling groups were lower compared to the control group (P<0.05). PAI-1 levels were lower in the double PTE group one and two hours after the second modeling compared to the other two groups and pre-modeling period (P<0.05). 3) The immunohistochemistry results: the expression of PAI-1 decreased in the two modeling groups, while t-PA expression increased compared to the control group. 4) PCR results: t-PA mRNA expression did not differ among the three groups. The PAI-1 mRNA expression was lower in the two PTE groups compared to the control group. We conclude that in the early stages of PTE, the local fibrinolytic activity of the thrombus is increased, which is favorable for thrombolysis. However, as the thrombus persists, the activity of the fibrinolytic system is inhibited, contributing to the development of chronic thromboembolic pulmonary hypertension.

Endovascular Recanalization of Symptomatic Chronic ICA Occlusion: Procedural Outcomes and Radiologic Predictors.

BACKGROUND AND PURPOSE: Endovascular recanalization has been attempted in patients with symptomatic chronic ICA occlusion, however, the heterogeneity of recanalization outcomes and the perioperative complications present challenges for the clinical application. Our aim was to evaluate the safety and efficacy of endovascular recanalization for symptomatic chronic ICA occlusion and identify potential predictors for successful recanalization. MATERIALS AND METHODS: This study included 47 consecutive patients with symptomatic chronic ICA occlusion who underwent endovascular recanalization at our institution. Patients' clinical information, radiologic characteristics, procedural results, and outcomes were recorded. Factors related to technical success were analyzed by univariate and multivariate analyses. RESULTS: The technical success rate was 74.5% (35/47); 12.8% of patients (6/47) experienced intraoperative complications, but none had permanent neurologic deficits. Three months after recanalization, 21 of the 29 recanalized patients (72.4%) and 3 of the 10 failed patients (30.0%) demonstrated improved mRS scores. Restenosis or re-occlusion occurred in 12.9% of patients (4/31) with successful recanalization. Multivariate analysis showed that tapered or blunt stump (P = .016), distal ICA occlusion segment (below the cavernous segment versus at or above the ophthalmic segment, P = .003; at the cavernous or clinoid segment versus at or above the ophthalmic segment, P = .027), and radiologic occlusion to recanalization of ≤3 months (P = .044) were significantly associated with successful recanalization. Patients were assigned points according to the coefficients of the prediction model, and the technical success rates were 0%, 46.2%, 90.5%, and 100% in patients with 1, 2, 3, and 4 points, respectively. CONCLUSIONS: Endovascular recanalization is a safe and effective treatment for symptomatic chronic ICA occlusion in selected patients. A residual stump, low levels of the distal ICA occlusion segment, and a short radiologic occlusion time were identified as positive predictors of technical success.

Automated Estimation of Quantitative Lesion Water Uptake as a Prognostic Biomarker for Patients with Ischemic Stroke and Large-Vessel Occlusion.

BACKGROUND AND PURPOSE: Net water uptake is qualified as an imaging marker of brain edema. We aimed to investigate the ability of net water uptake to predict 90-day functional outcome in patients with acute ischemic stroke and large-vessel occlusion. MATERIALS AND METHODS: A total of 295 consecutive patients were retrospectively enrolled. Automated ASPECTS-net water uptake was calculated on the admission CT. The relationship between ASPECTS-net water uptake and 90-day neurologic outcome was assessed. The independent predictors of favorable outcome (mRS score ≤2) were assessed using multivariate logistic regression analysis and receiver operating characteristic curves and stratified by the ASPECTS. RESULTS: Favorable 90-day outcomes were observed in 156 (52.9%) patients. ASPECTS-net water uptake (OR, 0.79; 95% CI, 0.70-0.90), NIHSS scores (OR, 0.91; 95% CI, 0.87-0.96), age (OR, 0.96; 95% CI, 0.94-0.99), and vessel recanalization (OR, 7.78; 95% CI, 3.96-15.29) were independently associated with favorable outcomes at 90 days (all, P < .01). A lower ASPECTS-net water uptake independently predicted a good prognosis, even in the subgroup of patients with low ASPECTS (≤5) (P < .05). An outcome-prediction model based on these variables yielded an area under the receiver operating characteristic curve of 0.856 (95% CI, 0.814-0.899; sensitivity, 76.3%; specificity, 81.3%). CONCLUSIONS: ASPECTS-net water uptake could independently predict 90-day neurologic outcomes in patients with acute ischemic stroke and large-vessel occlusion. Integrating ASPECTS-net water uptake with clinical models could improve the efficiency of outcome stratification.

Association between Infarct Location and Hemorrhagic Transformation of Acute Ischemic Stroke following Successful Recanalization after Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation. RESULTS: Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10; P = .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09; P = .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82; P < .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77; P = .002). CONCLUSIONS: Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage.

[Later approach sinus floor elevation using deproteinized bovine bone mineral with staged implant placement: follow-up for more than 3 years in a prospective clinical study].

Objective: To evaluate clinical effect of deproteinized bovine bone for delayed implantation after fenestration. Methods: This trial is a continuation of a prospective clinical trial. From May 2011 to February 2015 in Department of Implantology, School of Stomatology, The Fourth Military Medical University after planting division of 55 cases of maxillary teeth missing area of residual alveolar bone height ≤5 mm patients. There were 21 female and 34 male patients, their average age were (55.2±7.1) years. A total of 62 side fenestration of maxillary sinus floor lift, clinical and imaging examination, evaluation of implant retention rate, complications, peripheral soft tissue health and marginal bone resorption. Results: A total of 82 implants were followed up in 41 patients. The average follow-up time was (51.8±14.3) months (36-78 months). The follow-up rate of the maxillary sinus was 75.8% (47/62), the follow-up rate of the implant was 73.9% (82/111), and the implant survival rate was 98.8% (81/82). The bone resorption results at the implant margins were (0.64±0.63) mm (-0.28 mm, 1.47 mm) in the near and (0.49±0.73) mm (-0.51 mm, 1.21 mm) in the far, the improved hemorrhage index was 0.46±0.72, the improved plaque index was 0.60±0.87, and the keratinized mucosa width was (2.14±1.22) mm. The incidence rate of peri-implant mucositis was 28.4% (23/81) among 23 implants, and there was no complication of peri-implant inflammation. Conclusions: This study shows that under the condition of insufficient sinus ridge spacing in the maxillary posterior area, it is feasible to use bovine bone alone to remove protein for delayed implantation of maxillary sinus floor elevation by windowing, and the clinical effect is reliable.

[Establishment of animal model of bacterial microleakage at implant-abutment interface].

Objective: To study the bacterial microleakage at the interface between dental implant and abutment in rats. Methods: Under aseptic conditions, suspension of 0.25 µl of Porphyromonas gingivalis (Pg) (10(9) CFU/ml) was added into the customized implant. After the abutment was connected, the suspension was cultured in an Ep (eppendorf) tube containing 1 ml brain heart infusion (BHI) culture medium. After 7 days and 14 days, the liquid in the Ep tube was taken and inoculated, and the growth of bacteria was observed. Six male SD rats with 12 implants were divided into experimental group (4 implants), negative control group (4 implants) and blank control group (4 implants). All 6 rats had two implants implanted in their bilateral upper jaws. During the second operation, suspension of 0.25 µl Pg (10(9) CFU/ml) was added to the inner part of the implant of the experimental group, culture solution of 0.25 µl was added to the control group and nothing was added to the blank control group. The amount of Pg and total bacteria in each group were evaluated by quantitative real-time PCR (qPCR). The inflammatory cell infiltrate in the peri-implant mucosa was evaluated histomorphometrically. Results: The in vitro model directly verified the presence of bacterial microleakage at implant-abutment interface (IAI), and the animal model confirmed the existence of microleakage through the infiltrate of inflammatory cells near the micro-gap in the experimental group indirectly. In vitro experiments found that Pg had penetrated from the implant within a week by observation and culture. In animal study, the presence of 10(2)-10(4) Pg was detected in the experimental group and it was not detected in the negative control group and the blank control group. At the same time, under the light microscope, in the experimental group, there were inflammatory cells aggregation in the connective tissue around the micro-gap and the density of inflammatory cells gradually decreased from the micro-gap to coronal and the apical of the connective tissue, while there were only scattered inflammatory cells in the connective tissue around the blank control group and the negative control group. In the experimental group, inflammatory cells density in area of 0.25-0.50 mm, 0-0.25 mm coronal to the micro-gap and 0-0.25 mm, 0.25-0.50 mm apical to the mico-gap was respectively, 976 (655), 1 673 (1 245), 2 267 (819) and 895 (162) cells/mm(2),which was significantly more than the blank control group in the corresponding position [respectively 201 (180), 321 (351), 309 (236) and 218 (272) cells/mm(2)] (P<0.05). Conclusions: Pg in the dental implants of rats can be found in the microleakage through implant-abutment interface, and cause the soft tissue inflammation around the implant, and the inflammation has certain distribution characteristics.

[Application of polyetheretherketone and its composite as frameworks in fixed dental prostheses].

Characterized by eminent mechanical properties, chemical stability and biosafety, polyetheretherketone (PEEK), as a brand-new type of biomedical material, has been applied in the field of stomatology. This review elaborates on basic behaviors and fabrication methods of PEEK and its composite, and their application in fixed dental prostheses (FDP) as frameworks as well as their adhesive properties. Meanwhile, this review also looks into the prospect of the integration of additive manufacturing in fabricating frameworks of PEEK and its composite in FDP.

Risk of Acute Kidney Injury with Consecutive, Multidose Use of Iodinated Contrast in Patients with Acute Ischemic Stroke.

Currently, CTA is the imaging technique most frequently used to evaluate acute ischemic stroke, and patients with intracranial large-vessel occlusion usually undergo endovascular treatment. This single-center, prospective, cohort study showed that consecutive, multidose use of contrast during CTA and DSA does not increase the incidence of acute kidney injury in patients with acute ischemic stroke, though acute kidney injury tended to have a higher incidence in the contrast multiexposure group (P = .172).

Identification and quantitation of HIV-1 in the liver of patients with AIDS.

OBJECTIVE: To detect and quantify HIV-1 in the liver in vivo. DESIGN: Fourteen liver biopsy samples and corresponding blood lymphocytes and monocytes from patients with AIDS were studied for HIV-1 using quantitative polymerase chain reaction (PCR). In addition, expression of HIV-1 antigen and messenger (m) RNA in 10 autopsy liver specimens was examined by immunohistochemistry and in situ hybridization. RESULTS: The amount of HIV-1 DNA in nine liver samples ranged from 850 to 27,000 copies per 10(6) cells, with mean and median values of 8150 and 3500 copies per 10(6) cells, respectively. Five other samples had no detectable HIV-1 DNA by PCR. Intracellular expression of HIV-1 antigen and mRNA was also detected in both Kupffer cells and hepatocytes by in situ studies. CONCLUSION: These findings strongly indicate that HIV-1 could replicate in the liver of a majority of patients with AIDS.

Altered eicosanoid biosynthesis in selenium-deficient endothelial cells.

Selenium (Se) is an integral part of the Se-dependent glutathione peroxidase (Se-GSH-Px) catalytic domain. By modulating the cellular levels of fatty acid hydroperoxides, Se-GSH-Px can influence key enzymes of arachidonic acid cascade, in this case cyclooxygenase (COX) and lipoxygenase (LOX). To investigate this phenomenon, the effects of cellular Se status on the enzymatic oxidation of arachidonic acid were investigated in bovine mammary endothelial cells (BMEC), which were cultured in either Se-deficient (-Se) or Se-adequate (+Se) media. When stimulated with calcium ionophore A23187, BMEC produced eicosanoids of both COX and LOX pathways. Compared with the Se-adequate cells, the production of prostaglandin I(2) (PGI(2)), prostaglandin F(2) (PGF(2alpha)), and prostaglandin E(2) (PGE(2)) was significantly decreased in Se-deficient cells, whereas the production of thromboxane A(2) (TXA(2)) was markedly increased in the -Se BMEC cultures. Although the enzymatic oxidation of arachidonic acid by the LOX pathway was found to be relatively less than by the COX pathway, the BMEC cultured in -Se media produced significantly more 15-hydroperoxyeicosatetraenoic acid (15-HPETE) than the +Se cells produced. Based on these results, we postulate that cellular Se status plays an important regulatory role in the enzymatic oxidation of arachidonic acid by the COX and LOX pathways. The altered eicosanoid biosynthesis, especially the overproduction of 15-HPETE, in -Se BMEC may be one of the underlying biochemical phenomena responsible for vascular dysfunction during Se deficiency.

Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells.

Selenium (Se) is an integral component of glutathione peroxidase and is able to detoxify peroxides that can affect arachidonic acid (AA) metabolism, thereby influencing eicosanoid biosynthesis. This study investigated the effects of oxidant stress, a consequence of Se deficiency, on eicosanoid formation and important key enzyme expression in bovine aortic endothelial cells (BAEC). Bovine aortic endothelial cells cultured in Se-deficient media and stimulated with tumor necrosis factor alpha or H2O2 produced significantly less prostacyclin (PGI(2)) and more 15-hydroxyeicosatetraenoic acid, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), and thromboxane than Se-supplemented BAEC. Additionally, reverse transcription polymerase chain reaction and immunoblotting determined that the mRNA and protein levels of the eicosanoid forming enzymes cyclooxygenase-1 (COX1), cyclooxygenase-2 (COX2), and PGI synthase were not significantly changed. The addition of 15-HPETE to Se-supplemented BAEC inhibited the production of PGI(2) suggesting that the accumulation of lipid hydroperoxides during Se-deficiency may be the underlying factor in the altered eicosanoid production during Se deficiency. Furthermore, inhibition of COX and addition of PGH(2) to Se-deficient or Se-supplemented BAEC still resulted in lower PGI(2) formation by Se-deficient cells. Together, these results suggest that Se deficiency modifies eicosanoid production by affecting the activity of key enzymes, particularly PGI synthase, rather than their transcription or translation.

Selenium modulates 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) biosynthesis in bovine aortic endothelial cells.

Selenium (Se) deficiency has been reported to increase platelet-activating factor (PAF) production in human endothelial cells; however, the mechanism is unclear. This study demonstrated that tumor necrosis factor-alpha (TNF-alpha) stimulated Se-deficient bovine aortic endothelial cells (BAEC) produced significantly more PAF than Se-supplemented cells. Moreover, the increase in the level of PAF was associated with enhanced activity of two anabolic enzymes in the remodeling pathway: phospholipase A2 and Lyso-PAF:acetyl-coenzyme A acetyltransferase (Lyso-PAF-AcT). In contrast, the activity of the PAF catabolic enzyme, PAF-acetylhydrolase, was not affected by Se status. Interestingly, prostacyclin, a potent vasodilator and inhibitor of platelet aggregation, inhibited the activity of Lyso-PAF-AcT and reduced the PAF production in TNF-alpha-stimulated BAEC. Therefore, we conclude that Se deficiency alters PAF production in TNF-alpha-stimulated BAEC by altering the activity of anabolic enzymes involved in the remodeling pathway partially through the inhibition of prostacyclin production.

HIV-1 neutralizing antibodies in urine from seropositive individuals.

HIV-1 neutralizing activity was demonstrated in serum and 200-fold concentrated urine from individuals who were HIV-1 antibody positive in both their serum and urine, including AIDS-KS, AIDS-OI, ARC, and asymptomatic patients. Virus neutralization activity was detected in 23 of 56 (41.1%) of the serum samples and in 19 of 56 (33.9%) of the urine samples tested, with titers ranging from 1:8 to 1:256 and 1:1 to 1:4, respectively. The highest frequency of HIV-1 neutralizing activity (87.5%) and the highest mean neutralization titers (1:65) were found in the ARC patients. A high prevalence of p24 antigen in serum and low numbers of T4-lymphocytes correlated with a low frequency of neutralizing activity in either serum or urine in the infected individuals. HIV-1 neutralizing activity in the urine was shown to be due to immunoglobulins using a Sephadex G-100 filtration gel. All 19 urine samples with neutralizing activity contained antibodies reactive with envelope glycoproteins gp160, gp120, and gp41 by Western blot, similar to that seen with serum. The frequency of HIV-1 neutralizing activity in the urine concentrates was generally associated with high titers of neutralizing antibody in the corresponding serum. These findings suggest that HIV-1 neutralizing antibodies are lost in the urine by an as yet unknown mechanism.