Добірка наукової літератури з теми "628.161; 546.726"

AbstractMonoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9–8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2–1.2) and pembrolizumab (1.1%; 95% CI, 0.5–2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction – particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4–9.8; pembrolizumab, 8.5%; 95% CI, 7.5–9.7; PD-L1, 5.5%; 95% CI, 4.4–6.8; ipilimumab, 3.8%; 95% CI, 2.6–5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2–16.4%), hyperthyroidism (9.4–10.4%), hypophysitis (8.8–10.5%), and primary adrenal insufficiency (5.2–7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

We utilized 5-s changes of neck pressure and neck suction (from 40 to -80 Torr) to alter carotid sinus transmural pressure in seven men with peak oxygen uptake (VO2peak) of 41.4 +/- 3.6 ml O2.kg-1.min-1. Peak responses of heart rate (HR) and mean arterial pressure (MAP) to each carotid sinus perturbation were used to construct open-loop baroreflex curves at rest and during exercise at 25.7 +/- 1.1 and 47.4 +/- 1.9% VO2peak. The baroreflex curves were fit to a logistic function describing the sigmoidal nature of the carotid sinus baroreceptor reflex. Maximal gain for baroreflex control of HR (-0.31 +/- 0.05 beats.min-1.mmHg-1) and MAP (-0.30 +/- 0.08 mmHg/mmHg) at rest was the same as during exercise at 25 and 50% VO2peak (-0.30 +/- 0.05, -0.39 +/- 0.13 beats.min-1.mmHg-1 for HR, P = NS; -0.23 +/- 0.04, -0.60 +/- 0.38 mmHg/mmHg for MAP, P = NS). Resetting of the baroreflex occurred during exercise at 50% VO2peak. The centering point, threshold, and saturation pressures were significantly increased for baroreflex control of HR (delta pressure = 26.3 +/- 6.8, 19.6 +/- 10.4, 33.0 +/- 5.6 mmHg, P < 0.05) and MAP (delta pressure = 27.1 +/- 7.7, 16.1 +/- 14.8, 38.2 +/- 8.5 mmHg, P < 0.05). The operating point (steady-state HR and MAP) was shifted closer to threshold of the baroreflex during exercise at 50% VO2peak, as reflected by differences in HR and MAP between the centering and operating points (delta HR = 12.5 +/- 4.7 beats/min, P = 0.10; delta MAP = 7.6 +/- 1.3 mmHg, P < 0.05). These findings suggest a resetting of the carotid baroreflex during exercise with no attenuation in maximal sensitivity. A shift in operating point toward threshold of the baroreflex enables effective buffering of elevations in systemic blood pressure via reflex alterations in HR and MAP.

The aim: Develop a classification of post-traumatic soft tissue defects of the hand to standardize the care of this group of patients. And in order to simplify the choice of plastic technic for post-traumatic soft tissue defects of the hand by surgeons and traumatologists. Materials and methods: We analyzed the treatment of 54 patients with hand injury and PTSTD. 14 physicians used AFC in the choice of surgical method for the closure of PTSTDH. The practical application of AFC and effectiveness of providing medical care to patients with PTSTDH was performed on a ten-point scale by anonymous questioning immediately at the time of discharge from the hospital and 6 months after the injury. Results: The results of the practical application analysis of AFC by physicians were as follows: «convenience» – 8.7 ± 0.6; «usefulness» is 9.4 ± 0.2. The results of treatment for 54 patients were: hands «functionality» – 8,3 ± 0,4, «aesthetics» – 7,6 ± 1,7. The results in the retrospective group, in which the AFC was not applied, were as follows: «functionality» – 6.8 ± 0.7, and «aesthetics» – 5.6 ± 1.1 Conclusions: The proposed AFC of PTSTDH help to choose the proper method of surgical management and get good results.

AbstractObjectiveTo determine the prevalence of high weight at different characteristics, understand the perceptions and behaviours towards high body weight, and determine potential influencing factors of body weight misperception among high-weight adults in Jilin Province.DesignA cross-sectional survey with complex sampling design was conducted. We described the prevalence and perception of high body weight.SettingNortheast China in 2012.SubjectsAdults (n 20 552) aged 18–79 years.ResultsOf overweight individuals, 37·4 % considered themselves as ‘normal weight’, 4·8 % reported themselves as being ‘very thin’ and only 53·1 % were aware of their own weight being ‘overweight’. About 1·8 % of both male and female obese individuals perceived themselves as ‘very thin’. Only 29·1 % of obese people thought of themselves as ‘too fat’. Nearly 30·0 % of centrally obese men and women perceived that their waist circumference was about right and they were of ‘normal weight’; 5·7 % of the centrally obese even perceived themselves as being ‘very thin’. Only 51·8 and 12·5 % of centrally obese individuals reported themselves to be ‘overweight’ or ‘too fat’. Body weight misperception was more common in rural residents (OR; 95 % CI: 1·340; 1·191, 1·509). The prevalence of body weight misperception increased with age (middle age: 1·826; 1·605, 2·078; old people: 3·101; 2·648, 3·632) and declined with increased education level (junior middle school: 0·628; 0·545, 0·723; senior middle school: 0·498; 0·426, 0·583; undergraduate and above: 0·395; 0·320, 0·487).ConclusionsBody weight misperception was common among adults from Jilin Province.

e22519 Background: Global actions on pediatric cancer control is targeting to improve the survival rates in low and middle income countries which already exceeded 80% in high income countries. Almost 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Pediatric cancer registry must be a priority within the pediatric cancer control programs. Here, we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2020 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 12 years from 2009 to 2020, 21792 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 12198/9584, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.9%; 5-9 yrs, 23.7%; 10-14 yrs, 23.4%; 15-19 yrs, 12.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5208, 23.9%, 5.5, 3004/2204); Lymphoma & other RES tumors (4103, 18.8%, 9.8, 2733/1367, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3269, 15.0%, 6.8, 1794/1474, 1 unkown); Symphatetic system (1794, 8.2%, 2.4, 933/861); Retinoblastoma (610, 2.8%, 1.4, 339/271); Renal (1079, 5.0%, 3.1, 524/553, 1 hermaphrodite & 1 unknown); Liver (376, 1.7%, 2.2, 216/160); Malignant bone (1448, 6.6%, 12.5, 787/661); Soft tissue sarcomas (1554, 7.1%, 7.6, 888/666); Germ cell (1461, 6.7%, 9.3, 547/910, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (745, 3.4%, 13.5, 362/383); Other/non-specific malignant (145, 0.7%, 7.9, 71/74). Five year survival rate was found as 72%. Conclusions: This registry shows the imrovement of survival rates to 72% in Turkey which is comparable with middle income countries. The pediatric cancer control community is investing on the control of childhood cancer for further improvement and this registry became a valuable source for pediatric oncology community at national and international level.

11085 Background: Gene-expression signatures were shown to be prognostic and predictive for breast cancer but their performances over time have not been investigated. Methods: Recurrence score (RS) of oncotype, 70-gene profile (SGP) of Mammaprint, intrinsic subtype (IS) and wound signature (WS) were analyzed using a single dataset of 295 samples from Fan et al. (Fan et al. N Engl J of Med 2006; 355:560–9). Time-varying coefficient Cox models were used to estimate the time-dependent hazard ratios (HR) for relapse-free survival (RFS). Annualized RFS hazard rates were estimated using cubic splines. Concordance between RS and SGP was calculated for different intrinsic subtypes in all 295 samples and was evaluated in a subset of 173 ER+ samples not in the training set of SGP for unbiased comparison. Results: For the high risk groups of RS, SGP, IS and WS, hazard rates peaked around the 2nd year from surgery and decreased rapidly over time. For the low risk groups, hazard rates also peaked around the 2nd yr but remained fairly constant over time. Hazard ratios of high vs. low risk groups of RS at yr 2, 5 and 10 were 17.0 (8.4–34.0), 4.0 (2.0–8.0), 1.7 (0.83–3.4). For intermediate vs. low risk groups of RS, the corresponding HRs were 2.7 (1.1–7.0), 5.0 (1.1–7.4), 1.6 (0.63–4.2). Poor vs. good groups of SVP had HRs of 7.4 (4.5–12.1), 3.6 (2.2–5.9), 2.0 (1.2–3.3) at yr 2, 5, 10. HRs of Luminal B (LB), Basal-like (BL), HER2/ER- (HER2), Normal-like (NL) vs. Luminal A (LA) of Intrinsic Subtypes were 6.8 (4.0–11.5), 5.7 (3.2–10.0), 7.6 (4.0–14.1) and 1.7 (0.9–3.3) at yr 2. HRs at yr 5 were 4.0 (2.3–6.8), 0.7 (0.4–1.2), 1.1 (0.6–2.0) and 2.3 (1.2–4.4) respectively. For WS, HRs at yr 2, 5, 10 were 6.3 (3.3–11.9), 2.9 (1.6–5.6) and 2.2 (1.2–4.1) respectively. Concordance rates of RS and SVP were 1.0, 0.91, 0.86, 0.72 and 0.62 for BL, HER2, LB, LA, NL of Intrinsic Subtypes. In 173 ER+ samples not present in the SGP training set, concordance rate between RS and SVP was 0.77 (Cramer's V = 0.56); the same as in the whole set of 225 ER+ patients (Fan et al. N Engl J of Med 2006; 355:560–9). Conclusions: Prognostic values of gene-expression signatures decrease over time. They can best predict breast cancer relapse during the first 5 years. Concordance between RS and SPV is highest in the basal-like tumors and lowest in the Luminal B and Normal-like subtypes. No significant financial relationships to disclose.

Objective To determine risk factors affecting time-to-death ≤90 and >90 days in children who underwent a modified Blalock-Taussig shunt (MBTS). Methods Data from a retrospective cohort study were obtained from children aged 0–3 years who experienced MBTS between 2005 and 2016. Time-to-death (prior to Glenn/repair), time-to-alive up until December 2017 without repair, and time-to-progression to Glenn/repair following MBTS were presented using competing risks survival analysis. Demographic, surgical and anesthesia-related factors were recorded. Time-to-death ≤90 days and >90 days was analyzed using multivariate time-dependent Cox regression models to identify independent predictors and presented by adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results Of 380 children, 119 died, 122 survived and 139 progressed to Glenn/repair. Time-to-death probability (95% CI) within 90 days was 0.18 (0.14–0.22). Predictors of time-to-death ≤90 days (n = 63) were low weight (<3 kg) (HR 7.6, 95% CI:2.8–20.4), preoperative ventilator support (HR 2.7, 95% CI:1.3–5.6), postoperative shunt thrombosis (HR 5.0, 95% CI:2.4–10.4), bleeding (HR 4.5, 95% CI:2.1–9.4) and renal failure (HR 4.1, 95% CI:1.5–10.9). Predictors of time-to-death >90 days (n = 56) were children diagnosed with pulmonary atresia with ventricular septal defect and single ventricle (compared to tetralogy of fallot) (HR 3.2, 95% CI:1.2–7.7 and HR 3.1, 95% CI:1.3–7.6, respectively), shunt size/weight ratio >1.1 vs <0.65 (HR 6.8, 95% CI:1.4–32.6) and longer duration of mechanical ventilator (HR 1.002, 95% CI:1.001–1.004). Shunt size/weight ratio ≥1.0 (vs <1.0) and ≥0.65 (vs <0.65) were predictors for overall time-to-death in neonates and toddlers, respectively (HR 13.1, 95% CI:2.8–61.4 and HR 7.8, 95% CI:1.7–34.8, respectively). Conclusions Perioperative factors were associated with time-to-death ≤90 days, whereas particular cardiac defect, larger shunt size/weight ratio, and longer mechanical ventilation were associated with time-to-death >90 days after receiving MBTS. Larger shunt size/weight ratio should be reevaluated within 90 days to minimize the risk of shunt over flow.

Maddox Dairy, located in Riverdale, CA, USA, is a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg, and they have been producing high genetic animals by embryo transfer (ET) since the early 1980s. Invivo-derived embryos from Holstein donors were transferred fresh (grade 1 or 2) or frozen (grade 1), at morula (4), early blastocyst (5), or blastocyst (6) stage, to virgin heifers (VH, natural oestrus, 13-15 months old) or lactating cows (LC, Presynch-Ovsynch, 86 days in milk, first or second lactation) 6 to 9 days after oestrus. Pregnancy diagnosis was done by transrectal ultrasonography at 32-46 days in VH and by the IDEXX PAG test at 30 days in LC. June, July, August, September, and October were called critical months (first service AI conception rate drops below 44%) and compared with the other months. The data from 32 503 ETs between January 2008 and December 2018 are summarised on Table 1. Pregnancy rates (PR) are lower for LC recipients than for VH. Embryo transfers performed 7 or 8 days after oestrus had higher PR in both types of recipients and embryos, but Day 6 and 9 oestrus are also used with fair results. The season does not seem to affect PR. There is not enough difference in the combination of stage and days from oestrus for invivo-derived embryos. These numbers do not belong to a planned experiment. Several management changes during the years were made, which make it very difficult to apply statistical methods to analyse the data correctly. They are used as a tool to make decisions in an attempt to improve future results. Table 1.Pregnancy rate (PR) of virgin heifers (top) and lactating cows (bottom)-fresh (SH) and frozen (OZ) invivo-derived embryo transfer1 Heat-months SH-ST4 SH-ST5 SH-ST6 SH-All OZ-ST4 OZ-ST5 OZ-ST6 OZ-All PR% n PR% n PR% n PR% n PR% n PR% n PR% n PR% n Heifers 6 d-CM 62 934 66 243 68 69 63 1246 56 473 58 219 62 42 57 734 6 d-OM 62 1623 67 489 69 211 64 2323 56 600 55 296 48 137 55 1033 6 d-T 62 2557 67 732 69 280 63 3569 56 1073 57 515 51 179 56 1767 7 d-CM 64 1506 68 495 67 221 65 2222 60 822 62 340 63 156 61 1318 7 d-OM 66 2723 68 1021 69 510 67 4254 57 1120 59 581 57 231 58 1932 7 d-T 66 4229 68 1516 69 731 67 6476 58 1942 60 921 60 387 59 3250 8 d-CM 65 1348 64 518 67 322 65 2188 59 595 64 258 63 108 61 961 8 d-OM 66 2166 68 886 70 510 67 3562 61 770 60 364 51 130 60 1264 8 d-T 66 3514 67 1404 69 832 66 5750 60 1365 62 622 56 238 60 2225 9 d-CM 60 109 56 43 70 20 60 172 60 5 33 6 50 4 47 15 9 d-OM 58 129 63 57 60 40 60 226 63 16 50 18 75 4 58 38 9 d-T 59 238 60 100 63 60 60 398 62 21 46 24 63 8 55 53 All-CM 64 3897 66 1299 67 632 65 5828 58 1895 61 823 63 310 60 3028 All-OM 65 6641 67 2453 69 1271 66 10 365 58 2506 58 1259 53 502 58 4267 All-T 65 10 538 67 3752 69 1903 66 16 193 58 4401 60 2082 57 812 59 7295 Lactating cows 6 d-CM 54 265 48 86 50 12 53 363 38 141 31 77 50 10 36 228 6 d-OM 49 463 52 203 45 56 50 723 46 101 48 54 59 27 48 182 6 d-T 51 728 51 289 46 68 51 1086 41 242 38 131 57 37 42 410 7 d-CM 54 755 59 274 56 103 55 1137 43 928 48 450 43 192 45 1570 7 d-OM 55 914 66 367 54 109 58 1393 46 1052 45 564 47 353 46 1969 7 d-T 55 1669 63 641 55 212 57 2530 45 1980 46 1014 46 545 45 3539 8 d-CM 63 252 68 82 76 33 65 368 48 219 56 80 42 33 50 332 8 d-OM 61 257 64 161 53 47 61 466 50 191 53 77 56 16 51 284 8 d-T 62 509 65 243 63 80 63 834 49 410 55 157 47 49 50 616 All-CM 56 1272 58 442 60 148 57 1868 44 1288 47 607 43 235 45 2130 All-OM 55 1634 62 731 51 212 56 2582 47 1344 46 695 48 396 47 2435 All-T 55 2906 60 1173 55 360 57 4450 45 2632 47 1302 46 631 46 4565 1ST=stage; CM=critical months (June, July, August, September, and October); OM=other months.

This research aims to study the hydrolysis of passion fruit peel using cellulase and its evaluation for ethanol production. Passion fruit peel is a fruit processing waste that has not been utilized properly. Passion fruit peel contains holo-cellulose (64% w/w), which can be converted into ethanol through hydrolysis followed by fermentation. Hydrolysis using cellulase is more efficient and its fermentation using yeast to produce ethanol is common. The hydrolysis is carried out at various enzyme ratios (3, 5, 7, and 9% v/v) and at temperature 30 oC, material concentration 5 g/100 mL, pH 4-5, and shaking speed 160 rpm. The kinetics chosen were heterogeneous models; they were the fractal model by Valjamae and Kopelman. Before being hydrolyzed, the essential oil and pectin in passion fruit peel were extracted, because the compositions were quite high; the results were around 16.23 and 11.36% w/w, respectively. The effect of the enzyme ratio to the sugar concentration by hydrolysis is very significant. At 9 h, the glucose concentration reached 45.38, 51.86, 60.50, 66.00 g/L at various enzyme ratios of 3, 5, 7, 9% v/v. During the hydrolysis, the glucose concentration continues to increase and starts to decrease after 9 h. Hydrolyzate solution fermentation obtained from hydrolysis in various enzyme ratios showed consistent results; the higher the enzyme ratio and glucose, and the higher the ethanol will be (5.6, 6.8, 7.6, and 8.9% v/v). The kinetics model by Valjamae is more appropriate to describe the enzymatic hydrolysis mechanism of passion fruit peel than Kopelman. The fractal exponent values obtained from Valjamae and Kopelman models were 0.28 and 0.27. In Valjamae model, the enzyme ratio rises, from 3 to 9% v/v, the rate constant rises from 0.22 to 0.53 1/h. In Kopelman model, the rate constant rises too, from 0.21 to 0.51 1/h.Keywords: bio-ethanol; cellulase; enzymatic hydrolysis; fractal kinetic; passion fruit peel

The aim of the study was to identify the peculiarities of neuropsychological indices disorders depending on changes in the level of constant potential in patients with occupational diseases as a result of physical factors.Materials and methods. The study involved 60 patients with vibration disease caused by local vibration (group I), 106 patients with vibration disease caused by combined exposure to local and general vibration (group II), 101 civil aviation pilots with an established diagnosis of professional sensorineural hearing loss (group III), and 50 healthy men (group IV, comparison group) who were not exposed to vibration and noise due to the specifics of their professional activities. Methods of neuro-energy mapping and neuropsychological testing were used.Results. In groups I–II, compared with group IV, an increase in local levels of constant potential (DC-potential level) in the central, right temporal, and central frontal parts of the brain (2.3 (6.5–3.8) mV; –0.3 (–2.1–2.1); 2.1 (–3.4–6.8) and –0.3 (–3.1–4.3); –2.24 (–6.4–3.8); 0.9 (–3.1–8.5) mV at p = 0.005, 0.007 and 0.004 respectively). Differences in the values of DC-potential level gradients in individuals of group III when compared with group IV reached the level of significance in the central, temporal, occipital leads relative to the central frontal (–5.0 (–13.1–3.8); –4.1 (–9.4–5.1); –2.1 (–10.9–6.6); –6.3 (–15.3–1.8) and 2.9 (–3.0–10.6); 2.2 (–4.5–13.8); 5.6 (–7.6–14.1); –1.4 (–7.5–3.9) mV at p = 0.008; 0.009; 0.009, and 0.007 respectively). Cognitive disorders in patients of groups I–III when compared with group IV correspond to a mild disorder of dynamic, constructive praxis and expressive speech (1.40 (0–1,6); 1.43 (0–1,7); 1.2 (0–1,5) and 0.3 (0–1); 0.2 (0–1); 0.06 (0–1) points at p = 0.008, 0.008 and 0.009 respectively).Conclusions. A common neurofunctional sign of a mild impairment of the cognitive sphere in occupational diseases caused by physical factors is an increase in direct current potential level in the frontal-central and parieto-occipital regions, predominantly of the left hemisphere of the brain.

Platelet-PA-Inhibitors can be released by thrombin, Col laaen( Col) and others.If they are physiologically important,inhibition of their release might facilitate thrombolysis.Intrinsic PA were tested in euclobulins (eug)of PPP and PPP+Washed platelets(WP) ,with and without aspirinf ASA) .treated with UK,SK and Col(20 atfd l2uo/ml) Results(mm2)were:euaPPP:232+78;+3×106WP/ul:217+71;+10%7ul:188+/5 +2×106MP/ul: 157+69:With UK:eugPPP:283+76;+3×l0517P/ul :234+69;+106 WP/ul :172+55;+2×l(PWP/ul :154+48; With SK:euoPPP:303+99;+3×l05WP/ul 252+65;+1067P/ul:203+68;+2×106UP/ul: 174+85;Wi th Col (20ug/ml) :eur PPP:234+97;+3×105WP/ul:160+63;+106WP/ul:141+73;+2×l06WP/ul:129+81; +2×106WP/ul+ASA: 105+31;Wi th Col uc/ml) :euaPPP:230+56;+3×l05NP/ul: 160+52;+106WP/ul:139+44;+2×106wp/ul:126+21;+2×106WP/ul+ASA:118+28. EugPPP+l/P showed lower lysis area.Col induced more decrease of lysis area in euc with WP.ASA did not modify this effect.UK and SK produced higher lysis area only in euoPPP.No difference was observed between high and low doses of Col-effect upon WP.Combined treatment of eucPPP+WP+Col, with UK and SK showed:(mm2):UK-treated eugPPP+2×106WP/ul+Col(29ug/ml):134+25;+ASA and Col(20ug/ml):115+65;+Col(2uc/ml):157+50;+ASA and Col(2uo/ml):133+49; SK-treated eupPPP+2×106WP/ul:+Col(20uo/ml):144+49;+ASA and Col(20ug/ml):128+ 60;+Co1(2ug/ml):173+66;+ASA and Col(2ug/ml):142+36.Col (20ug/ml) produced slight lower lysis area of UK and SK-treated eugPPP+WP. (p:ns). ASA did not modify this effect.Col (2uc/ml) did not produce changes in lysis area of UK and SK-treated eupPPP +WP. ASA produced slight lower lysis area(p:ns).Conclusion: high dosis of Col could release anti UK,anti SK and intrinsic PA-inhibitors from platelets;low dosis of Col could only release fntrinsic PA-inhibi tors. It suggests that anti UK and anti SK release might be triggered by stronger stimuli than intrinsic PA inhibitors.ASA could not inhibit any inhibitors release.We must consider that PA-inhibi tors could be released by different metabolic pathways other than cyclooxygenase pathway.

We have previously shown that the isolated perfused rat Langendorff heart is able to synthesize detectable amounts of thromboxane (TX) A2, as well as prostacyclin (PGI2). Eicosanoid production in this system is increased during post-ischemic reperfusion, reflecting greater availability of substrate and net increase of synthesis. We assessed relative sensitivity of cyclooxygenases synthesizing TX and prostacyclin (probably located in different cell types) to aspirin (0.1, 0.5, 1 g/1), ibuprofen (1, 10, 80, 160, 320 mg/1) and diclofenac (0.01, 0.1, 0.5, 2.5, 5, 10, 25 mg/1), by radioimmunoassays of TXB2 and 6-keto-PGFα in the perfusate. Sixty Wistar male rat hearts were perfused with buffer containing control vehicle or drugs for 30 min, followed by 5 min clamping of the perfusion line and subsequent post-ischemic reperfusion. Baseline production was (mean±SD, pg/min/g wet weight) 754±261 and 143±66 for PGI2 and TXA2, respectively. Peak post-ischemic production was 7628±2673 and 1036±135, respectively. At doses of aspirin, ibuprofen and diclofenac (100, 10 and 2.5 mg/1, respectively) which were equally effective on prostacyclin production (mean % inhibition: 68, 67 and 72 for basal production and 90, 86 and 85 for peak post-ischemic production, respectively), % inhibition of TX production was consistently less, but also similar for the three drugs: 55, 58 and 56 for basal production and 78, 81 and 76 for peak post-ischemic production, for aspirin, ibuprofen and diclofenac, respectively; difference between inhibition of prostacyclin and TX: P < .01, difference for subsets among different drugs: N.S.). TX production was, on the contrary, selectively inhibited by the TX-synthase inhibitor 0KY 046 (by 79 and 92% at 0.1 mg/1, versus a complete sparing of prostacyclin production). The lesser sensitivity of cardiac (vascular?) TX versus prostacyclin to non-steroidal antiinflammatory drugs (NSAIDs) inhibition and the similar degree of inhibition by various NSAIDs, differing in structure and diffusing capacity, suggest heterogeneity among cyclooxygenases present in the system and different intrinsic sensitivity of TX- from prostacyclin-producing cyclooxygenases.

The extract from the venom sac of Vespa orientalis (VSE) inactivates exogenous and endogenous thromboplastin (Joshua and Ishay, Toxicon, 13:11-20,1975). The prolongation of both prothrombin time (PT) and recalcification time suggests inactivation of other factors. The aim of the present study is to investigate the effect of VSE on clotting factors. A lyophilized VSE with protein concentration of 5 mg/ml was used. Studies were performed in vitro with human plasma and in vivo in cats. Routine methods were employed for the assay of PT, activated tissue thromboplastin (APTT), thrombin time (TT), fibrinogen degradation products (FDP), fibrinogen and factors V,VII,VIII,IX,X. Human plasma was incubated with various concentrations of VSE (0,1,5,10,50,100 μg/ml) for 60 min and for various incubation times (0,5,15,30,+ 60,90,120 min) with 50 μg/ml VSE (n=8). 1 μg/ml VSE prolonged PT from 13.5 to 16 sec (p<0.05) and APTT from 62 to 180 sec. PT was maximal (17.7 sec) with 10 μg/ml and APTT (442 sec) with 50 μg/ml VSE. Factors V,VII,X decreased gradually from 94-105% to 11%,11% and 29% with 100 μg/ml VSE and VIII and IX to 1% even with 1 μg/ml VSE. After 5 min with constant concentration of VSE (50 μg/ml) PT was 14.9 sec (normal 13 sec) and APTT 165 sec (normal 54 sec). Both were maximal (17.5 and 298 sec) after 60 min. Factors VII and X decreased to 13% and 32% and VIII and IX to >1% after 60 min of incubation. Injection of 5 mg/kg VSE to cats (n=6-8) resulted in prolongation of PT from 9.4 to 11.2 sec and of APTT from 19.5 to 63 sec after 5 min. Both were maximal after 90 min (12.3 and 127 sec). Factors V,VII and X decreased from 100% to 7.6%, 13% and 37% and VIII and IX to 1% after 10 min. In all experiments TT and plasma fibrinogen were not affected and FDP were normal. Heating of VSE for 5 min at 80°C abolished completely the anticoagulant activity but dialysis for 24 hr at 4°C had no effect on it. The activity was eluted on Sephadex-25 both in void and post void volumes. The results show that VSE has a potent anticoagulant activity against various factors. Factors VIII and IX are markedly decreased. The effect on V, VII and X is moderate. Plasma fibrinogen is not affected. The nature and clinical significance of the anticoagulant activity merit further investigation.