Effect of Bile on Hemodynamics and Blood Micro-Rheological Parameters in Experimental Models of Bilhemia.

As a rare complication of liver injury and certain interventions, bile can enter the bloodstream depending on the pressure gradient, resulting in bilhemia. Its micro-rheological and hemodynamic effects are still unclear. We aimed to study these parameters in experimental bilhemia models. Under general anesthesia, via laparotomy, bile was obtained by gallbladder puncture from pigs and by choledochal duct cannulation from rats. In vitro, 1 µL and 5 µL of bile were mixed with 500 µL of anticoagulated autologous blood. The systemic effect was also assessed (i.v. bile, 200 µL/bwkg). Hemodynamic and hematological parameters were monitored, and red blood cell (RBC) deformability and aggregation were determined. RBC deformability significantly decreased with the increasing bile concentration in vitro (1 µL: p = 0.033; 5 µL: p < 0.001) in both species. The RBC aggregation index values were concomitantly worsened (1 µL: p < 0.001; 5 µL: p < 0.001). The mean arterial pressure and heart rate decreased by 15.2 ± 6.9% and 4.6 ± 2.1% in rats (in 10.6 ± 2.6 s) and by 32.1 ± 14% and 25.2 ± 11.63% in pigs (in 48.3 ± 18.9 s). Restoration of the values was observed in 45 ± 9.5 s (rats) and 130 ± 20 s (pigs). Bilhemia directly affected the hemodynamic parameters and caused micro-rheological deterioration. The magnitude and dynamics of the changes were different for the two species.

Minor micro-rheological alterations in the presence of an artificial saphenous arteriovenous shunt, as an arteriovenous malformation model in the rat.

BACKGROUND: Arteriovenous malformations (AVMs) are vascular anomalies characterized by abnormal shunting between arteries and veins. The progression of the AVMs and their hemodynamic and rheological relations are poorly studied, and there is a lack of a feasible experimental model. OBJECTIVE: To establish a model that cause only minimal micro-rheological alterations, compared to other AV models. METHODS: Sixteen female Sprague Dawley rats were randomly divided into control and AVM groups. End-to-end anastomoses were created between the saphenous veins and arteries to mimic AVM nidus. Hematological and hemorheological parameters were analyzed before surgery and on the 1st, 3rd, 5th, 7th, 9th, and 12th postoperative weeks. RESULTS: Compared to sham-operated Control group the AVM group did not show important alterations in hematological parameters nor in erythrocyte aggregation and deformability. However, slightly increased aggregation and moderately decreased deformability values were found, without significant differences. The changes normalized by the 12th postoperative week. CONCLUSIONS: The presented rat model of a small-caliber AVM created on saphenous vessels does not cause significant micro-rheological changes. The alterations found were most likely related to the acute phase reactions and not to the presence of a small-caliber shunt. The model seems to be suitable for further studies of AVM progression.

A Custom-Tailored Multichannel Pressure Monitoring System Designed for Experimental Surgical Model of Abdominal Compartment Syndrome.

In experimental medicine, a wide variety of sensory measurements are used. One of these is real-time precision pressure measurement. For comparative studies of the complex pathophysiology and surgical management of abdominal compartment syndrome, a multichannel pressure measurement system is essential. An important aspect is that this multichannel pressure measurement system should be able to monitor the pressure conditions in different tissue layers, and compartments, under different settings. We created a 12-channel positive-negative sensor system for simultaneous detection of pressure conditions in the abdominal cavity, the intestines, and the circulatory system. The same pressure sensor was used with different measurement ranges. In this paper, we describe the device and major experiences, advantages, and disadvantages. The sensory systems are capable of real-time, variable frequency sampling and data collection. It is also important to note that the pressure measurement system should be able to measure pressure with high sensitivity, independently of the filling medium (gas, liquid). The multichannel pressure measurement system we developed was well suited for abdominal compartment syndrome experiments and provided data for optimizing the method of negative pressure wound management. The system is also suitable for direct blood pressure measurement, making it appropriate for use in additional experimental surgical models.

Impact Assessment of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Hemostatic Sponge on Vascular Anastomosis Regeneration in Rats.

The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration.

A Microsurgical Arteriovenous Malformation Model on Saphenous Vessels in the Rat.

Arteriovenous malformation (AVM) is an anomaly of blood vessel formation. Numerous models have been established to understand the nature of AVM. These models have limitations in terms of the diameter of the vessels used and the impact on the circulatory system. Our goal was to establish an AVM model that does not cause prompt and significant hemodynamic and cardiac alterations but is feasible for follow-up of the AVM's progression. Sixteen female rats were randomly divided into sham-operated and AVM groups. In the AVM group, the saphenous vein and artery were interconnected using microsurgical techniques. The animals were followed up for 12 weeks. Anastomosis patency and the structural and hemodynamic changes of the heart were monitored. The hearts and vessels were histologically analyzed. During the follow-up period, shunts remained unobstructed. Systolic, diastolic, mean arterial pressure, and heart rate values slightly and non-significantly decreased in the AVM group. Echocardiogram results indicated minor systolic function impact, with slight and insignificant changes in aortic pressure and blood velocity, and minimal left ventricular wall enlargement. The small-caliber saphenous AVM model does not cause acute hemodynamic changes. Moderate but progressive alterations and venous dilatation confirmed AVM-like features. The model seems to be suitable for studying further the progression, enlargement, or destabilization of AVM.

Heterogeneous Maturation of Arterio-Venous Fistulas and Loop-Shaped Venous Interposition Grafts: A Histological and 3D Flow Simulation Comparison.

Vascular graft maturation is associated with blood flow characteristics, such as velocity, pressure, vorticity, and wall shear stress (WSS). Many studies examined these factors separately. We aimed to examine the remodeling of arterio-venous fistulas (AVFs) and loop-shaped venous interposition grafts, together with 3D flow simulation. Thirty male Wistar rats were randomly and equally divided into sham-operated, AVF, and loop-shaped venous graft (Loop) groups, using the femoral and superficial inferior epigastric vessels for anastomoses. Five weeks after surgery, the vessels were removed for histological evaluation, or plastic castings were made and scanned for 3D flow simulation. Remodeling of AVF and looped grafts was complete in 5 weeks. Histology showed heterogeneous morphology depending on the distribution of intraluminal pressure and WSS. In the Loop group, an asymmetrical WSS distribution coincided with the intima hyperplasia spots. The tunica media was enlarged only when both pressure and WSS were high. The 3D flow simulation correlated with the histological findings, identifying "hotspots" for intimal hyperplasia formation, suggesting a predictive value. These observations can be useful for microvascular research and for quality control in microsurgical training.

Antioxidant and polyphenol content of different Vitis vinifera seed cultivars and two facilities of production of a functional bakery product.

This study aimed to examine the differences between the antioxidant capacity, and the total polyphenol content of the seed of eight different grape varieties. We also attempt to create a functional loaf enriched with grape seed meal. To achieve this goal, 3, 6, and 9% of the grape seed meal were added to the loaves made of bread flour and gluten-free flour mixture, and then the changes in their antioxidant and polyphenol content were examined. Based on the results, there were significant differences between the polyphenol and antioxidant content of grape seed varieties. The antioxidant content of the grape seeds varied between 228.50 mg AAE/g (94.80 mg TE/g) and 438.33 mg AAE/g (181.86 mg TE/g) in case of fatty samples, and between 176.29 mg AAE/g (41.24 mg TE/g) and 424.91 mg AAE/g (99.40 mg TE/g) in case of defatted samples. The total polyphenol content of the fatty samples changed between 91.16 and 221.81 mg GAE/g; in case of defatted samples, it ranged from 46.01 to 207.68 mg GAE/g. Rhine Riesling contained the greatest amount of these compounds. The functionality of loafs was confirmed by spectrophotometric analysis. Total polyphenol content ranged from 0.91 to 3.16 mg GAE/g in case of wheat loafs, and from 1.39 to 5.92 mg GAE/g in case of gluten-free loafs, while the total antioxidant content changed between 0.70 and 6.44 mg AAE/g in case of wheat loafs, and ranged from 2.55 to 9.75 in case of gluten-free loafs.

The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids.

OBJECTIVES: Ulipristal acetate is a selective progesterone receptor modulator that has been demonstrated to be an effective 3-month pre-operative treatment for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of 5mg ulipristal as an add-on therapy to standard pre-surgical observation and treatment in Hungary. STUDY DESIGN: A Markov model was developed using a 10-year time horizon. Ulipristal was compared with pre-surgical observation and immediate hysterectomy. The model comprised the following mutually exclusive health states: mild, moderate, severe, or persistent severe excessive bleeding disorder; myomectomy; post-myomectomy with mildly to moderately excessive bleeding disorder; post-myomectomy with severely excessive bleeding disorder; hysterectomy; post-hysterectomy; post-menopause; and death. Transition probabilities and utility values were obtained from clinical trials and the scientific literature. Resource utilisation and unit costs were derived from a consensus panel of clinical experts, National Health Insurance Fund tariffs, and publications. RESULTS: Adding a 3-month course of ulipristal to pre-operative observation was predicted to achieve an additional 0.021 quality-adjusted life years (QALYs) at an estimated incremental cost of €397, which would result in an incremental cost of €19,200/QALY. When 3 months of ulipristal therapy was compared with immediate hysterectomy, the incremental cost-effectiveness ratio was reduced to €3575/QALY. The results were most sensitive to the utility value of the post-hysterectomy health state but responsive to changes in other model parameters. CONCLUSIONS: The results of this analysis suggest that adding ulipristal treatment to standard pre-surgical therapy represents a good value for money in Hungary. The inclusion of societal benefits may considerably reduce the cost-effectiveness ratio.

[Obstetrical and gynecological relevance of inflammatory bowel disease]. / A gyulladásos bélbetegségek szülészeti-nogyógyászati vonatkozásai.

INTRODUCTION: Inflammatory bowel disease may show a life long persistence, while female fertility is time-limited. AIM: The aim of the authors was to obtain more knowledge about the obstetrical-gynecological aspects of this disorder. METHODS: The authors evaluated 100 patients with inflammatory bowel disease and 100 healthy women with a self-composed questionnaire. RESULTS: Menarche occurred significantly earlier in patients than in controls (p = 0,03). Either the activity of the disease, or the therapy itself may initiate irregularities in the menstrual cycle. Patients used contraceptives less frequently than controls (p = 0,002), and the time from family-planning to conception was longer in patients. Symptoms of bowel disease during pregnancy were not as severe as before and after pregnancy (p<0,001). Excess weight had a beneficial effect on symptoms during pregnancy (p = 0,042) and on the frequency of complications. Preterm birth and low birth weight were more frequent in newborns of patients (p = 0,019). CONCLUSION: Pregnancy has positive effect on the symptoms of inflammatory bowel disease in case gestation occurs in a stable period of the inflammatory bowel disease.

Analysis of platelet alpha2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy.

Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP), collagen and epinephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y(12)-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) - and in 24 subjects platelet P-selectin positivity were measured. Epinephrine - at very low concentration (10(-9)g/ml) - significantly potentiates (1.25 microM ADP: 26.5% vs. 43%; 5 microM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p < 0.001) while atipamezole inhibits ADP- and collagen-induced platelet aggregations (1.25 microM ADP: 26.5% vs. 23%; 5 microM ADP: 53% vs. 47%; collagen: 17% vs. 11%, p < 0.001). Patients with high adrenergic activity have significantly increased baseline ADP- and collagen-induced platelet aggregation. Based on cangrelor's efficacy, these patients have significantly more residual P2Y(12) activity as well. HsCRP and soluble CD40-ligand levels were similar. In conclusion, stable coronary heart disease patients with prominent adrenoceptor activity in vitro have significantly increased platelet aggregability and more functional P2Y(12) receptor, indicating poor inhibitory response to thienopyridines. Therefore, platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular events indicating failure of antiplatelet therapy.

The reliability of fetal pulse oximetry: the effect of fetal oxygen saturation below 30% on perinatal outcome.

OBJECTIVES: The objective of this prospective study was to determine the reliability of fetal pulse oximetry (FPO) in cases of abnormal fetal heart rate (FHR) pattern and fetal oxygen saturation (FSpO(2)) below 30%. STUDY DESIGN: Three hundred and one deliveries complicated by abnormal FHR pattern were monitored with both CTG and FPO. Cases of FSpO(2) values below 30% (n=52) formed the study group and those above 30% (n=249) were the control group. pH and base excess (BE) in the umbilical cord artery, 5-min Apgar score, and pH and BE in the newborn were measured and compared. Statistical analysis included the Epi info 2002 program, Chi-squared test, and linear regression. RESULTS: FSpO(2) values were consequently below 30% in 52 and above 30% in 249 cases. When FSpO(2) values were below 30%, umbilical pH was significantly lower than in controls (P<0.01), while other parameters were not significantly different. If the time interval between the measurement of the first low (<30%) FSpO(2) value and delivery did not exceed 32.4+/-2.5 min, umbilical pH and Apgar scores did not show fetal acidosis. CONCLUSION: Our findings suggest that FPO is a reliable method of estimating fetal condition and may help reduce the number of cesarean sections performed due to abnormal FHR tracings.

Recombinant human activated protein C treatment of septic shock syndrome in a patient at 18th week of gestation: a case report.

Recombinant human-activated protein C (rhAPC) has been suggested to treat sepsis. We present the case of a 19-year-old pregnant patient at the 18th week of gestation with septic shock syndrome that originated from urinary tract infection and was successfully treated with rhAPC.

[Postmenopausal osteoporosis]. / Osteoporosis a postmenopausában.

Due to its incidence and clinical consequences osteoporosis followed by vertebral, hip, and forearm fractures represents an outstanding problem of nowadays' health care. Because of its high mortality rate hip fractures are of special interest. The number of fractures caused by postmenopausal osteoporosis increases with age. Costs of examinations and treatment of women with postmenopausal osteoporosis and fractures are also increasing and represent a significant amount all over the world. Organization of Osteoporosis Centres in Hungary was founded in 1995 and has been since functioning, however, only the one-sixth of osteoporotic patients are treated. Several risk factors are known in the pathogenesis of osteoporosis, first of all the lack of sufficient calcium and vitamin D intake, age, genetic factors, and circumstances known to predispose falling. Estrogen deficiency is the most likely cause of postmenopausal osteoporosis. Osteodensitometry by DEXA is the most important method to evaluate osteoporosis, since decrease in bone mineral density strongly correlates with fracture incidence. Physical, radiologic, and laboratory examination are also required at the first visit and during follow-up. The quantity of bone can hardly be influenced after the 35th year of age, thus prevention of osteoporosis has special significance: appropriate calcium and vitamin D supplementation, weight-bearing sports and physical activity can prevent fractures. According to the results from studies fulfilling the criteria of evidence-based medicine, first choice treatment of osteoporosis involves hormone replacement therapy, bisphosphonates, the tissue specific tibolone, raloxifen and calcitonin. Calcium and vitamin D supplementation are always necessary to be added to any antiporotic treatment. Other combinations of different antiporotic drugs are useless and make the treatment more expensive. Other treatments like massage, physiotherapy, hip-protecting pants, etc. as well as rehabilitation have special clinical significance.