The effects of progesterone, prostaglandin F2α and oxytocin on the calcium-activation of the uterus

The relationship between “activator-calcium” (A-Ca), progesterone (P), prostaglandin F2α (PGF2α) and oxytocin (Oxy) has been examined in 100 uterine strips of 34 pregnant and 100 strips of 34 post partum rabbits. At the 25th day of gestation, uterine P was 13.9±1.3 ng/g, while within 3–12 hours post partum 3.3±0.3 ng/g tissue (P<0.001). Uterine strips, mounted isometrically in Krebs' solution, sustained maximum excitability in a steady state when exposed every 30 seconds for 4 seconds to an electric field of 12 V/5 cm (a.c.). The maximally contracting muscles were then rinsed at intervals of 6 minutes with Ca-free Krebs.In Ca-free Krebs, the post partum uterus lost 31% of its Ca and 96% of its excitability in a short 25 minutes, while the pregnant uterus lost 30% of its Ca and 93% of its excitability in 50 minutes (P<0.001). Since the extracellular space is 30% in the uterus, this 30% Ca, lost by both muscles, most probably was extracellular Ca and the small A-Ca fraction which is presumably “bound” more strongly at the membrane systems of the P-dominated pregnant, than the non-dominated post partum uterus. The significantly faster and more complete recovery from Ca-deficiency and inexcitability of the pregnant than the post partum uterus (P<0.001), at different levels of external Ca, further substantiates this premise. So does the demonstration that exposure to Ca-free Krebs increases ⁴⁵Ca-efflux 400% in the post partum and only 110% in the pregnant uterus (P<0.001). Exposure to 100 ng/ml PGF2α in normal Krebs has a similar effect on the ⁴⁵Ca-efflux of the post partum uterus, while the response of the pregnant uterus is indistinct (P<0.001).These highly significant differences between the post partum and the pregnant uteri in their Ca-efflux explain the higher threshold (P<0.001) and lower “sensitivity” to PGF2α and Oxy (P<0.001) of the pregnant than the post partum uterus. The already very highly significant differences between the two muscles, in threshold and sensitivity to these two most potent oxytocics, were increased still further by rendering the uterine strips Ca-deficient. All together, these findings substantiate the early contention (1–7,18,19) that uterine function at the cellular level is regulated by opposing actions of the suppressor P and the intrinsic stimulant PG or other oxytocic agents on threshold, excitability and the Ca-activation of the contractile process.     

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P<0.001), active pressure (P<0.001) and frequency (P<0.05) of cyclic activity of the uterus, as well as menstrual pain (P<0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.     

Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

Objective

Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD).

Approach and Results

Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by −50%, (both P<0.001). Simvastatin and the combination reduced total cholesterol (−30%; −55%, P<0.001) where the combination revealed a greater reduction compared to simvastatin (−36%, P<0.001). Niacin decreased total cholesterol and triglycerides primarily by increasing VLDL clearance. Niacin increased HDL-cholesterol (+28%, P<0.01) and mildly increased reverse cholesterol transport. All treatments reduced monocyte adhesion to the endothelium (−46%; −47%, P<0.01; −53%, P<0.001), atherosclerotic lesion area (−78%; −49%, P<0.01; −87%, P<0.001) and severity. Compared to simvastatin, the combination increased plaque stability index [(SMC+collagen)/macrophages] (3-fold, P<0.01). Niacin and the combination reduced T cells in the aortic root (−71%, P<0.01; −81%, P<0.001). Lesion area was strongly predicted by nonHDL-cholesterol (R² = 0.69, P<0.001) and to a much lesser extent by HDL-cholesterol (R² = 0.20, P<0.001).

Conclusion

Niacin decreases atherosclerosis development mainly by reducing nonHDL-cholesterol with modest HDL-cholesterol-raising and additional anti-inflammatory effects. The additive effect of niacin on top of simvastatin is mostly dependent on its nonHDL-cholesterol-lowering capacities. These data suggest that clinical beneficial effects of niacin are largely dependent on its ability to lower LDL-cholesterol on top of concomitant lipid-lowering therapy.     

Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects

Introduction

Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects.

Methods

The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO₂ (EtCO2) and end-tidal O₂ (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations.

Results

HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO₂ (+0.5; P<0.001) EtO₂ (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO₂ (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO₂(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO₂ (-0.7%; NS) and EtCO₂ (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations.

Conclusions

Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP—cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure.     

Aging Differentially Affects the Loss of Neuronal Dendritic Spine,Neuroinflammation and Memory Impairment at Rats after Surgery

It is known that age is an important factor for postoperative cognitive dysfunction (POCD) and the patients with POCD suffer from the impairment of multiple brain regions and multiple brain functions. However currently animal studies of POCD mainly focus on hippocampus region, therefore in this study we performed partial hepatectomy in young adult and aged rats to test the questions (1) whether POCD in animals involves other brain areas besides hippocampus; (2) how age influences POCD of young adult and aged animals. We found that (1) in young adult rats, the memory was not significantly affected (P>0.05) 1d, 3d and 7d after partial hepatectomy, but was significantly impaired (p<0.001) in aged rats 1d and 3d post-surgery; (2) in young adult rats, the surgery did not significantly affect the densities of dendritic spines of neurons at CA1, dentate gyrus (DG) and cingulate cortex (P>0.05, respectively) 1d and 3d post-surgery, but the spine densities at CA1 and DG of aged rats were significant reduced 1d and 3d post-surgery (p<0.001, respectively), however this didn’t happen at cingulate cortex (P>0.05); (3) In young adult rats, surgery didn’t affect the activation of microglia and levels of TNF-α and IL-1β at hippocampus (P>0.05), but significantly activated microglia and increased levels of TNF-α and IL-1β at hippocampus of aged rats (P<0.05). Our data suggest that (1) partial hepatectomy-induced POCD mainly involves hippocampus impairments, and (2) differential loss of neuronal dendritic spines and neuroinflammation at hippocampus are most likely the mechanism for the formation of POCD in aged rats.     

Imbalance of Pro- vs. Anti-Coagulation Factors in Chinese Patients with Budd-Chiari Syndrome and Non-Cirrhotic Portal Vein Thrombosis

Background and Aim

The coagulation abnormalities in non-cirrhotic Budd-Chiari syndrome (NC-BCS) and non-cirrhotic portal vein thrombosis (NC-PVT) are unclear. We conducted this case-control study to investigate the coagulation profile of NC-BCS and NC-PVT in Chinese patients.

Methods

We measured the levels of factors II, V, VII, VIII, IX, X, XI, XII, protein C (PC), protein S (PS) and antithrombin (AT) in blood samples from 37 NC-BCS patients, 74 NC-PVT patients, and 100 healthy controls. The levels and ratios of pro- and anti-coagulation factors were compared between patients with NC-BCS and healthy controls, between different types of NC-BCS and between NC-PVT and healthy controls.

Results

In patients with NC-BCS, factor VIII (P<0.001) was significantly elevated; factor V (P<0.001), VII (P<0.001), IX (P = 0.003), X (P<0.001), XI (P<0.001), XII (P<0.001), PC (P<0.001) and AT (P<0.001) were significantly decreased; and no difference was observed for factor II (P = 0.088) and PS (P = 0.199) compared with healthy controls. Factor VIII-to-PC (P = 0.008), factor VIII-to-PS (P = 0.037) and factor VIII-to-AT (P = 0.001) were significantly increased; other ratios were significantly reduced or did not show any difference. No differences were observed between different types of NC-BCS for individual pro- and anti-coagulation factors or the ratios between them. Among patients with NC-PVT, factor VIII (P<0.001) was significantly elevated and other factors were significantly decreased. Factor II-to-PC (P<0.001), factor VIII-to-PC (P<0.001), factor IX-to-PC (P<0.001), factor VIII-to-PS (P<0.001), factor II-to-AT (P<0.001), factor VIII-to-AT (P<0.001) and factor IX-to-AT (P<0.001) were significantly increased; all other ratios for NC-PVT were significantly reduced or did not show any significant difference.

Conclusions

NC-BCS and NC-PVT are associated with elevated levels of factor VIII and the decreased levels of PC and AT were probably the most significant features of coagulation imbalance. Additionally, NC-PVT was associated with decreased levels of PS.     

The effect of feeder type and change of feeder type on growing and finishing pig performance and behaviour

Reduced feed intake and hence lower growth rates commonly occur when the environment of the pig changes, e.g. at weaning and when pigs are moved from growing accommodation to finishing accommodation. It is hypothesised that if environmental factors, such as feeder type, remain the same in the weaning and finishing accommodation this ‘growth check’ may be reduced. A total of 640 pigs in 32 pens of 20 pigs per pen were used to investigate the effects of two feeder types and changing or not changing the feeder type at 10 weeks of age on growth performance and behaviour in the periods from 4 to 10, 10 to finish (22) and from 4 to finish (22) weeks of age, respectively. The two feeder types tested were a ‘wet and dry’ single-space (S) feeder and a ‘dry’ multi-space feeder (M).In the period 4–10 weeks of age feeder type had no significant effect on growth performance though pigs on the ‘dry’ multi-space feeder tended to exhibit significantly better feed efficiency from 4 to 7 weeks of age. In the first week after changing accommodation the growth rate of pigs on all treatments was depressed (compared to the last 3 weeks of the grower period) and was reduced a further 60 g/day when the feeder type was changed. However, the “feeder” effect was transitory and had no effect on overall finisher performance except for pigs changed from a ‘dry’ multi-space feeder to ‘wet and dry’ single-spaced feeder. These animals had significantly faster growth rate over the finisher phase (P<0.05, 886 g/day) and between 4 weeks of age and finish (P<0.05, 730 g/day) than pigs on all other treatments. Feeder treatment had no significant effect on feed intake or feed efficiency in the finisher period or overall from wean to finish. Similarly, the treatments had no effect on the variation in growth rate. Behavioural observations showed that the average number of pigs at the feeder during the finishing period was significantly higher when feed was offered from treatment M–S (1.19 (freq/30 s), P<0.001). In conclusion, the present results suggest that, a change in feeder type, from a ‘dry’ multi-space feeder in growing accommodation to a ‘wet and dry’ single-space feeder in finishing accommodation appears to stimulate improved growth performance in the early finishing period and overall from weaning to finish.     

The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis

Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatoryrelated pathways in apolipoprotein E knockout (apoE^−/−) mice with diabetic atherosclerosis. Forty-five male apoE^−/− mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorizedtreadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339±75.613×10³µm²) compared to the control (325.485±72.302×10³ µm²) and sedentary (340.188±159.108×10³µm²) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE^−/− mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.Key words: diabetes, atherosclerosis, exercise, matrix metalloproteinases, plaque stability.     

Coagulation and Fibrinolysis Index Profile in Patients with ANCA-Associated Vasculitis

Background

Previous studies observed the high prevalence of venous thromboembolism in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study analyzed the coagulation and fibrinolysis index profile in AAV patients.

Methods

The current study recruited 321 AAV patients in active stage and 78 AAV patients in quiescent stage. Coagulation and fibrinolysis index profiles in these AAV patients were analysed, and their associations with various clinical and pathological parameters were further investigated.

Results

The circulating levels of D-dimer, fibrin degradation products and platelet count were significantly higher in AAV patients in active stage compared with those in remission [0.8 (0.4, 1.5) mg/L vs. 0.28 (0.2, 0.55) mg/L, P<0.05; 5.6 (5.0, 10.0) mg/L vs. 1.9 (1.2, 2.8) mg/L, P<0.05; 269±127×10⁹/L vs. 227±80×10⁹/L, P<0.05, respectively]. Among the 321 AAV patients in active stage, compared with patients with normal levels of D-dimer, patients with elevated D-dimer levels had significantly higher levels of initial serum creatinine, erythrocyte sedimentation rate, C reactive protein and the Birmingham Vasculitis Activity Scores (P = 0.014, P<0.001, P<0.001, P = 0.002, respectively). Moreover, correlation analysis showed that the levels of D-dimer correlated with erythrocyte sedimentation rate and C reactive protein levels (r = 0.384, P<0.001; r = 0.380, P<0.001, respectively).

Conclusion

Patients with active AAV are in hypercoagulable states, and circulating levels of D-dimer are associated with disease activity of AAV.     

The effects of ovariectomy and strech on the regulatory profile and activity of the uterus

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 μg PGF2α provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P<0.001) and the PG levels had not changed significantly, 50 μg PGF2α significantly increased cyclic IUP as compared with the day 25 value (P<0.001). At day 27, when the P levels decreased further, as little as 5 μg PGF2α provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P<0.05).Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P<0.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.     

Vitamin D and Exercise Performance in Professional Soccer Players

Aim

The current study had two aims. The primary purpose was to examine the association between serum vitamin D levels and the ergometric evaluation of muscle strength, aerobic capacity, and speed in professional soccer players. The secondary aim was to evaluate the effects of the soccer off-season period on serum vitamin D levels.

Methods

Sixty-seven Caucasian male soccer players (age 25.6±6.2 and height 1.81±0.08 m), members of two Greek Superleague Soccer teams and one Football-league championship team participated in this study. Exercise performance testing for the determination of squat jump (SJ), countermovement jump (CMJ), 10 (10 m) and 20 meters (20 m) sprint performance, maximal oxygen consumption (VO₂max), anthropometry, and blood sampling were performed before (pre) and after (post) the six-week off-season period.

Results

Analysis of our results showed the following: (a) a significant correlations between serum vitamin D levels and performance parameters in both pre (SJ; P<0.001, CMJ; P<0.001, VO₂max; P<0.001, 10 m; P<0.001, and 20 m; P<0.001) and post (SJ; P<0.001, CMJ; P<0.001, VO₂max; P = 0.006, 10 m; P<0.001, and 20 m; P<0.001) experimental sessions. (b) Vitamin D concentration increased significantly (P<0.001) following the six-week off-season period compared to baseline, while at the same time all measured performance parameters decreased (SJ; P<0.001, CMJ; P<0.001, 10 m; P<0.001, 20 m; P<0.001, VO₂max; P<0.001).

Discussion

Our findings suggest that vitamin D levels are associated with the ergometric evaluation of muscle strength, as expressed by SJ and CMJ, sprinting capacity, and VO₂max in professional soccer players, irrespective the levels of performance. Furthermore, our data reaffirm the importance of UVB on serum vitamin D levels. Moreover, reductions in exercise training stress may also have beneficial effects on vitamin D levels, suggesting a possible association of its levels and the training-induced stress. Our results indicate a possibly bidirectional interaction between soccer performance indices and vitamin D levels.     

Intraocular Pressure and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

Purpose

To examine a potential association between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in a population-based setting.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP [mm Hg] = 0.44×Body Mass Index [kg/m²]+0.16×Diastolic Blood Pressure [mm Hg]–0.18×Age [Years].

Results

In multivariate analysis, IOP was associated with higher estimated CSFP (P<0.001; standardized correlation coefficient beta: 0.27; regression coefficient B: 0.20; 95% confidence interval (CI): 0.16, 0.24), after adjusting for thinner central corneal thickness (P<0.001; beta: 0.45; B: 0.04;95%CI: 0.04,0.04), smaller corneal curvature radius (P<0.001; beta:−0.11; B:−1.13;95%CI:−1.61,−0.64), shallower anterior chamber depth (P = 0.01; beta:−0.05; B:−0.33;95%CI:−0.59,−0.08) and longer axial length (P = 0.002; beta: 0.08; B: 0.20;95%CI: 0.08,0.32)), and after adjusting for the systemic parameters of higher pulse rate (P<0.001; beta: 0.08; B: 0.02;95%CI: 0.01,0.03), higher prevalence of arterial hypertension (P = 0.002; beta: 0.06; B: 0.32;95%CI: 0.12,0.53)), frequency of drinking alcohol (P = 0.02; beta: 0.04; B: 0.09;95%CI: 0.01,0.17), higher blood concentration of triglycerides (P = 0.001; beta: 0.06; B: 0.06;95%CI: 0.02,0.10) and cholesterol (P = 0.049; beta: 0.04; B: 0.08;95%CI: 0.00,0.17), and body mass index (P<0.001; beta:−0.13; B:−0.09;95%CI:−0.13,−0.06). In a parallel manner, estimated CSFP (mean: 10.8±3.7 mm Hg) was significantly associated with higher IOP (P<0.001; beta: 0.13; B: 0.18;95%CI: 0.13,0.23) after adjusting for rural region of habitation (P<0.001; beta:−0.37; B:−2.78;95%CI:−3.07,−2.48), higher systolic blood pressure (P<0.001; beta: 0.34; B: 0.06;95%CI: 0.05,0.07), higher pulse rate (P = 0.003; beta: 0.05; B: 0.02;95%CI: 0.01,0.03), taller body height (P<0.001; beta: 0.11; B: 0.05;95%CI: 0.03,0.07), higher blood concentration of cholesterol (P = 0.003; beta: 0.05; B: 0.17;95%CI: 0.06,0.28) and higher level of education (P = 0.003; beta: 0.09; B: 0.30;95%CI: 0.16,0.45).

Conclusions

IOP was positively associated with estimated CSFP after adjusting for other ocular and systemic parameters. As a corollary, higher estimated CSFP was significantly associated with higher IOP in multivariate analysis. It fits with the notion that the arterial blood pressure, estimated CSFP and IOP are physiologically correlated with each other.     

Whey Protein Reduces Early Life Weight Gain in Mice Fed a High-Fat Diet

An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001–0.05). Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001). Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01) and glucose clearance was improved after an oral glucose challenge (P<0.05). Plasma cholesterol was lowered by whey compared to casein (P<0.001). The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05) whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey.     

Influence of enzyme supplementation of diets and cooking–flaking of maize on digestive traits and growth performance of broilers from 1 to 21 days of age

A trial was conducted to study the influence of cooking–flaking (C-F) of maize and enzyme supplementation (ES) of the diet on mucosa morphometry, digestive organ weight, dietary component digestibility and growth performance of broilers from 1 to 21 days of age. There were 4 treatments arranged factorially with 2 heat processings of maize (raw and C-F) and 2 levels (0 and 500 mg/kg) of an enzyme complex with xylanase, protease and α-amylase activity. Dietary treatment did not affect any productive trait from 1 to 21 days of age. However, from 1 to 4 days of age, body weight gain (P<0.01) and feed conversion ratio (P<0.001) were improved by ES of the diet. Intestinal viscosity increased with C-F of maize and decreased with ES of the diet (P<0.001). The effects of ES on intestinal viscosity were more pronounced with C-F than with raw maize (P<0.001) and at younger than older ages (P<0.05). Cooking–flaking of maize increased total tract apparent digestibility of dry matter and organic matter (P<0.05) and of neutral detergent fibre and starch (P<0.001) and tended to improve ether extract (EE) digestibility (P<0.10). In addition, ES improved nitrogen retention (P<0.01) and EE digestibility (P<0.001). Digestibility of neutral detergent fibre and starch increased linearly (P<0.001) with age whereas nitrogen retention and organic matter, EE and gross energy digestibility decreased from 4 to 8 days of age and increased thereafter (P<0.001). The relative weight (g/kg body weight) of the pancreas decreased (P<0.01) and that of the liver increased (P<0.001) with C-F of maize. The relative weight of the proventriculus, gizzard and liver reached a maximum before 6 days of age and that of the small intestine and pancreas at approximately 7.8 days of age (P<0.001). Enzymes increased villus height (P<0.05) but did not affect villus width or villus surface area. It is concluded that C-F of maize improved dietary component digestibility but had no effect on broiler performance at 21 days of age. In addition, ES improved nitrogen retention, EE digestibility and productive performance of broilers but only from 1 to 4 days of age.     

C1 Esterase Inhibitor Reduces Lower Extremity Ischemia/Reperfusion Injury and Associated Lung Damage

Background

Ischemia/reperfusion injury of lower extremities and associated lung damage may result from thrombotic occlusion, embolism, trauma, or surgical intervention with prolonged ischemia and subsequent restoration of blood flow. This clinical entity is characterized by high morbidity and mortality. Deprivation of blood supply leads to molecular and structural changes in the affected tissue. Upon reperfusion inflammatory cascades are activated causing tissue injury. We therefore tested preoperative treatment for prevention of reperfusion injury by using C1 esterase inhibitor (C1 INH).

Methods and Findings

Wistar rats systemically pretreated with C1 INH (n = 6), APT070 (a membrane-targeted myristoylated peptidyl construct derived from human complement receptor 1, n = 4), vehicle (n = 7), or NaCl (n = 8) were subjected to 3h hind limb ischemia and 24h reperfusion. The femoral artery was clamped and a tourniquet placed under maintenance of a venous return. C1 INH treated rats showed significantly less edema in muscle (P<0.001) and lung and improved muscle viability (P<0.001) compared to controls and APT070. C1 INH prevented up-regulation of bradykinin receptor b1 (P<0.05) and VE-cadherin (P<0.01), reduced apoptosis (P<0.001) and fibrin deposition (P<0.01) and decreased plasma levels of pro-inflammatory cytokines, whereas deposition of complement components was not significantly reduced in the reperfused muscle.

Conclusions

C1 INH reduced edema formation locally in reperfused muscle as well as in lung, and improved muscle viability. C1 INH did not primarily act via inhibition of the complement system, but via the kinin and coagulation cascade. APT070 did not show beneficial effects in this model, despite potent inhibition of complement activation. Taken together, C1 INH might be a promising therapy to reduce peripheral ischemia/reperfusion injury and distant lung damage in complex and prolonged surgical interventions requiring tourniquet application.     

A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×10⁹/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×10⁹/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.     

The Impact of National Institutes of Health Funding on U.S. Cardiovascular Disease Research

Background

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

Methods

The National Library of Medicine''s PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases “cardiolog,” “cardiovascular,” or “cardiac,” in the first author''s department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance.

Results

Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomized-controlled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001).

Conclusions

NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact.     

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual periods, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay.The patients receiving placebo had high PGF levels 135 ± 27 ng/ml (Mean ± S.E.) which were significantly reduced by Ibuprofen to 24 ± 5 ng/ml (P<0.001). The PGE concentrations decreased from 5 ± 1 ng/ml to 2 ± 1 ng/ml (P<0.05). Ibuprofen also reduced the menstrual pain significantly (P<0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.     

Histomorphometric analysis of adult articular calcified cartilage zone

The aim of this study was to carry out a histomorphometric analysis of calcified cartilage zone (CCZ) and its interfaces between hyaline cartilage and subchondral bone. The study used 40 donated normal human femoral condyles, from which paraffin-embedded sections were prepared after fixation and decalcification. The histomorphology of the CCZ were qualitatively and quantitatively observed by staining, scanning electron microscopy (SEM) and three-dimensional (3D) reconstruction. The hyaline cartilage and CCZ were stained red with Safranin-O, and the subchondral bone was stained blue with Fast green. CCZ was stained black after von Kossa staining. The hyaline cartilage was interlocked tightly in the manner of “ravine-engomphosis” by the CCZ. The surface roughnesses of tidemark and cement line were 1.14 ± 0.04 and 1.99 ± 0.38. The maximum, minimum and mean thicknesses of CCZ were 277.12 ± 8.6, 9.83 ± 6.72 and 104.162 ± 0.87 μm, respectively. The cell density of CCZ (51.25 ± 21.26 cells/mm²) was significantly lower than that of the hyaline cartilage (152.54 ± 35.77 cells/mm²) (P < 0.05). The subchondral bone was anchored tightly in the manner of a “comb-anchor” by the CCZ in our 3D reconstruction model. Thus, we discovered two junctional interfaces of CCZ using different histomorphometric methods. The upper interface of CCZ is a “ravine-engomphosis” shape, while its lower interface is a “comb-anchor” shape.     

The efficacy of the extraovular “Prostaglandin-Impact” in provoking first trimester abortion

In good agreement with earlier findings (1–8) legal abortion had been induced successfully with Csapo's method of “Prostaglandin Impact” (PGI) in 44 out of 50 sedated patients. They were 25±1.1 years of age, 11.3±0.2 weeks pregnant, para 1.1±0.2. Only a PGI (10 mg PG F2α) was delivered into the extraovular space. In 44 women, this single PGI provoked 40% progesterone (P)-withdrawal in 3 hours (P < 0.001) and 64% P-withdrawal (P < 0.001) in 15.3±0.9 hours, when the patients aborted. The remaining 6 women, whose P-withdrawal was only 14% at 3 hours without continuation during 24 hours, failed to abort. Thus in PG-induced abortions the regulatory significance of rapid and continued P-withdrawal (1–8) had been verified.The side effects were mild, transient and acceptable. The “Abortion Score” was 86. There were no serious complaints or complications during the study and followup. Since even in the 6 cases of failure the cervix dilated sufficiently to allow curettage (without surgical dilatation), the therapeutic benefits of the single PGI technique should be further examined in those services, where constant medical supervision (for determining the necessity and timing of repeated PGI) is not available.