Tamoxifen decreases ovarian toxicity without compromising cancer treatment in a rat model of mammary cancer.

BACKGROUND: Premenopausal women diagnosed with breast cancer often face aggressive chemotherapy resulting in infertility. Tamoxifen (TAM) is a selective estrogen receptor modulator that was previously suggested as a protective agent against chemotherapy-induced ovarian failure. In the current study, we examined mechanisms of the protective action of TAM in the ovaries of tumor-bearing rats treated with the chemotherapy drug cyclophosphamide (CPA). RESULTS: TAM prevented CPA-induced loss of ovarian follicular reserves. The protective TAM effect in the rat ovary partially resulted from decreased apoptosis. In addition, transcriptomic and proteomic screening also implicated the importance of DNA repair pathways as well as cell adhesion and extracellular matrix remodeling in the protective ovarian actions of TAM. CONCLUSIONS: Tamoxifen shielded the ovary from the side effects of chemotherapy without lessening the tumoricidal actions of mammary cancer treatment.

Isoprostane-8 and GDF-15 as novel markers of post-PE syndrome: Relation with prothrombotic factors.

BACKGROUND: Post-pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. OBJECTIVE: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post-PE syndrome. METHODS: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5-7 days and after a 3-month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8-isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks ), along with PE biomarkers, were determined. RESULTS: Patients who developed the post-PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N-terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor-1 as compared to subjects without post-PE syndrome (all P < .05). After 5-7 days, only hypofibrinolysis was noted in post-PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post-PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor-1 (all P < .05). 8-isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63-12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29-12.16) measured at 3 months were associated with higher risk of developing post-PE syndrome. CONCLUSIONS: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post-PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome.

COVID-19 pandemic influence on epilepsy course in pediatric patients.

INTRODUCTION: In 2020, Coronavirus Disease 2019 (COVID-19) was declared as a global pandemic. Self-reported stress, anxiety, and insomnia, which are believed to be common triggers for epilepsy, are more likely to occur. We aimed to establish the influence of COVID-19 pandemic itself on changes in the daily life routine related to pandemic on epilepsy course in pediatric patients. The unique form of clinical care which is telemedicine was also taken into consideration. We wanted to evaluate patients' satisfaction with telemedicine and if changing stationary visits into telemedicine influenced epilepsy course in our patients. METHODS: Patients, who attended developmental neurology outpatient clinic in the period March-December 2020 were collected. As patients were minors, legal guardians were asked to fill out the questionnaire. Patients were divided according to the outcome into three groups: those with a worsened, stable, or improved course of epilepsy during the pandemic. Appropriate statistical tests for two-group and multi-group comparisons have been implemented. Post hoc p values were also calculated. RESULTS: Four hundred and two questionnaires were collected. Most of the patients had a stable course of epilepsy during the pandemic; in 13% of participants an improvement has been observed, worsening of the disease was seen in 16% of patients. Age, sex, type of epilepsy, number of seizure incidents before pandemic, and duration of the disease had no statistically significant connection with changes in the course of the disease. Behavioral changes and altered sleep patterns were found to be more common in the worsened group. Fifty-eight percent of patients were satisfied with telemedicine. Poorer satisfaction was connected with less frequent visits, cancellation of scheduled appointments, and lack of help in case of need in an emergency situation. CONCLUSION: Epilepsy course in pediatric patients seems to be stable during COVID-19 pandemic. Sleep disturbances and changes in a child's behavior may be related to increase in seizure frequency. Telemedicine is an effective tool for supervising children with epilepsy. Patients should be informed about possible ways of getting help in urgent cases.

Comparison of the Efficacy and Safety of Two Dosing Protocols for Ultrasound Guided Thrombin Injection in Patients with Iatrogenic Femoral Pseudoaneurysms.

OBJECTIVE: Ultrasound guided thrombin injection (UGTI) is a minimally invasive method of treatment for iatrogenic post-catheterisation femoral pseudoaneurysms (psAs). The optimal dosing protocol for UGTI has not been established. The aim of the study was to compare the success and complication rates between two different dosing protocols (the most commonly used "standard dose protocol" and the "low dose protocol," which is the fractionated administration of smaller thrombin doses of up to 40 IU every 15 s) in patients with a psA with sac volume of ≥1 mL. METHODS: This was a retrospective cohort study, and the analysis was performed using a case matching approach based on propensity score. From June 2004 to August 2018, 384 patients who underwent femoral puncture for transcatheter procedures were diagnosed with femoral psA with a sac volume of ≥1 mL and qualified for UGTI. The patients' mean age was 68 (±10.6) years and there were 217 (56.5%) women. To compare protocols, 124 patients treated according to the low dose protocol were nearest neighbour matched according to their propensity score to 124 patients treated according to the standard dose protocol. RESULTS: The overall success rate (99.2% vs. 98.4%; p = 1) and success rate of the first UGTI attempt (87.1% vs. 86.3%; p = .85) did not differ between the low dose and standard dose groups. Complications were less common in the low dose group (7.3% vs. 16.1%; p = .03) and the median total amount of thrombin used for procedures was smaller in the low dose group (120 IU vs. 195 IU; p = .01). CONCLUSIONS: In patients with femoral psA with sac volume of ≥1 mL, the use of the low dose protocol seemed to be equally effective as the standard dose protocol and was associated with a lower complication rate and reduced thrombin dose.

Global peak left atrial longitudinal strain assessed by transthoracic echocardiography is a good predictor of left atrial appendage thrombus in patients in sinus rhythm with heart failure and very low ejection fraction - an observational study.

BACKGROUND: Peak left atrial longitudinal strain (PALS) can help identify left atrial appendage thrombus (LAAT) in patients with atrial fibrillation. Nevertheless, few studies have been performed in patients in sinus rhythm without established indications for anticoagulation but with increased risk of LAAT, such as heart failure (HF) with severe left ventricular systolic dysfunction patients. The primary aim of this study was to identify clinical and transthoracic echocardiography predictors of LAAT in HF patients with very low left ventricular ejection fraction and sinus rhythm. The secondary objective was to analyze frequencies and predictors of a composite clinical endpoint of death or hospitalization for ischemic stroke. METHODS: We included 63 patients with HF, left ventricular ejection fraction < 25%, sinus rhythm at presentation, no history of atrial fibrillation, and without any established indications for anticoagulation. We determined whether clinical and transthoracic echocardiography parameters, including left atrial strain analysis, predicted LAAT. Transesophageal echocardiography was performed in all patients. When LAAT was detected, anticoagulation was recommended. The participants were followed for a median of 28.6 months (range 4-40) to determine the composite endpoint. RESULTS: LAAT was found in 20 (31.7%) patients. Global PALS was the best independent predictor of LAAT in univariate and multivariate logistic regression analyses (Gini coefficient 0.65, area under the receiver-operating characteristic curve 0.83). A global PALS value below 8% was a good discriminator of LAAT presence (odds ratio 30.4, 95% CI 7.2-128, p <  0.001). During follow-up, 18 subjects (28.6%) reached the composite clinical endpoint. CHA2DS2-VASc score, use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, and body surface area were significant predictors for the composite endpoint of death or hospitalization for ischemic stroke in the multivariate regression model. CONCLUSIONS: LAAT was relatively common in our group of HF patients and PALS has shown prognostic potential in LAAT identification. Further research is needed to determine whether initiation of anticoagulation or additional screening supported by PALS measurements will improve clinical outcomes in these patients.

Altered Fibrin Clot Properties Predict Stroke and Bleedings in Patients With Atrial Fibrillation on Rivaroxaban.

Background and Purpose- We investigated whether clot permeability can predict clinically relevant outcomes in patients with atrial fibrillation (AF) treated with rivaroxaban. Methods- In the cohort study, we enrolled 232 consecutive patients with AF on rivaroxaban 20 mg/d (76.3%) or 15 mg/d (23.7%) for at least 3 months. Plasma clot permeability (Ks), a measure of fibrin network density, was determined 24 to 30 hours since the intake of rivaroxaban at undetectable drug's levels. Ischemic cerebrovascular events and bleedings were recorded. Results- During a median follow-up of 48 months, patients with Ks below median (6.8 cm2·10-9) had higher prevalence of stroke (5.84 versus 0.88% per year; P<0.0001) and relevant bleeding (7.06 versus 0.88% per year; P<0.0001) compared with those above median. The mortality rate was 1.53% per year and was not associated with Ks. Lower Ks predicted cerebrovascular ischemic events (hazard ratio, 6.64; 95% CI, 2.2-20.1) and relevant bleedings (hazard ratio, 7.38; 95% CI, 2.58-21.10). Minor bleeds (32.8% of patients) were observed more often in patients with Ks above median (50.9 versus 14.7%; P<0.0001). Multivariate Cox regression analysis showed that in AF patients on rivaroxaban lower Ks increased the risk of stroke (hazard ratio, 6.51; 95% CI, 2.14-19.75) and relevant bleedings (hazard ratio, 9.68; 95% CI, 3.21-29.18). Conclusions- Decreased clot permeability in AF patients can predict thromboembolic and clinically relevant bleeding events during therapy with rivaroxaban, while looser clot networks predispose to minor bleeds.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Thrombocytopenia.

AIMS: Thrombocytopenia was one of the exclusion criteria in randomized trials in which non-vitamin K antagonist oral anticoagulants (NOACs) were tested. The safety of NOACs in patients with atrial fibrillation (AF) and thrombocytopenia remains unclear. METHODS: We studied 62 patients with AF aged from 53 to 85 (mean 70.5) years with platelet count from 50 to 100 × 109/L who were treated with rivaroxaban 15 mg once daily (33.9%), dabigatran 110 mg twice daily (bid) (54.8%), or apixaban 2.5 mg bid (11.3%). Age- and sex-matched AF patients with normal platelet count and similar CHA2DS2-VASc scores who were treated with the recommended doses of NOACs served as a reference group. RESULTS: Patients were followed for a mean of 55 months (range, 23-64 months). In the thrombocytopenia group bleeding risk was higher (mean HAS-BLED score 2.0, vs. 1.0, P < 0.0001). During follow-up in thrombocytopenic and normocytopenic patients, we observed similar rates of major bleeding (1.8%/year vs. 2.7%/year, P = 0.49), clinically relevant nonmajor bleeding (CRNMB) (1.5%/year vs. 1.1%/year, P = 0.74), ischemic stroke and transient ischemic attacks (1.8%/year vs. 1.5%/year, P = 0.8), and death (1.06%/year vs. 1.11%/year, P = 0.96). The risk of bleeding and stroke was unaffected by the type of the NOAC used in both groups. Major bleedings and clinically relevant nonmajor bleeding in thrombocytopenic patients on NOACs were predicted only by age (hazard ratio 1.1, 95% confidence interval 1.0-1.3, P = 0.04). CONCLUSIONS: Our findings indicate that in AF patients with mild thrombocytopenia, anticoagulation with NOAC at reduced doses seems to be safe and effective.

Target-Agnostic Identification of Functional Monoclonal Antibodies Against Klebsiella pneumoniae Multimeric MrkA Fimbrial Subunit.

The increasing incidence of Klebsiella pneumoniae infections refractory to treatment with current broad-spectrum antibiotic classes warrants the exploration of alternative approaches, such as antibody therapy and/or vaccines, for prevention and treatment. However, the lack of validated targets shared by spectrums of clinical strains poses a significant challenge. We adopted a target-agnostic approach to identify protective antibodies against K. pneumoniae Several monoclonal antibodies were isolated from phage display and hybridoma platforms by functional screening for opsonophagocytic killing activity. We further identified their common target antigen to be MrkA, a major protein in the type III fimbriae complex, and showed that these serotype-independent anti-MrkA antibodies reduced biofilm formation in vitro and conferred protection in multiple murine pneumonia models. Importantly, mice immunized with purified MrkA proteins also showed reduced bacterial burden following K. pneumoniae challenge. Taken together, these results support MrkA as a promising target for K. pneumoniae antibody therapeutics and vaccines.

[Membranous nephropathy - the most commonly diagnosed glomerulopathy in patients who underwent renal biopsy in the Department of Internal Medicine, Nephrology and Endocrinology St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszow].

We retrospectively analysed the results of 120 renal biopsy, performed in 52 women, 62 men and 6 children hospitalized mainly in the Department of Internal Medicine, Nephrology and Endocrinology St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszów from 2013 to 2016. The average age of patients on whom renal biopsy was performed amounts to 44 (7-78) years. The most common indications for renal biopsy were nephrotic syndrome in 47 patients (37.3%), non-nephrotic proteinuria in 31 patients (24.6%), worsening renal function in 22 patients (17.5%), coexistence proteinuria with hematuria in 16 patients (12.7%), nephritic syndrome in 9 patients (7.1%) as well as an isolated hematuria in 1 patient (0.8%). Membranous glomerulonephritis was the most common histological diagnosis observed in biopsies, and was diagnosed in 19 patients (15.1%). In 14 patients we diagnosed lupus nephritis (11.1%). With the same frequency we diagnosed focal glomerulosclerosis, and mesangioproliferative glomerulonephritis (11 patients, 8,7%). Membraneproliferative glomerulonephritis was diagnosed in 10 patients (7.9%). Other nephropathy accounted for less than 8% of all diagnoses. Most patients with membranous nephropathy (8 patients, 61%) had antibodies against phospholipase A2 receptor. All patients with a diagnosis of membranous nephropathy received the renin- angiotensin-aldosterone system blockade, and 13 patients (68.4%) received immunosuppressive therapy. Complete remission was achieved in 11 patients (64.7%) with primary membranous nephropathy. In 35 patients (27.8%) of all patients who underwent renal biopsy they had complications after procedure in the form of small and clinically insignificant perirenal hematomas. Hematuria was observed in 7 cases (5.56%). In one case, due to retroperitoneal bleeding, the patient required a transfusion of blood products.

The Effect of Coumestrol on Progesterone and Prostaglandin Production in the Mare: In Vitro and In Vivo Studies.

Coumestrol (Cou) is a plant-derived phytoestrogen that induces various pathologies in the female reproductive tract. Although effects of phytoestrogens on reproductive function in other species are well documented, their influence on progesterone (P4) and prostaglandin (PG) secretion in the mare is unknown. The aim of this study was to determine if Cou directly affects P4 and PG concentrations (in vivo) and endometrial PG secretion (in vitro) in the mare. In experiment 1, the mares (n = 4) were fed for 14 days on a diet containing increasing proportions of alfalfa pellets (250 g-1 kg/day). An additional 4 mares were fed a standard diet (control group). Sequential blood samples were obtained for 8 h after feeding on Days 13 and 14 (1 kg/day alfalfa pellets). Feeding the mares alfalfa pellets up-regulated PGE2 and 13,14-dihydro-15-ketoprostaglandin F2alpha (PGFM) and down-regulated P4 in the blood plasma compared to those in the control group (P < 0.05). In experiment 2, epithelial and stromal cells were exposed to E2 (10-9 M) or Cou (10-8 M) for 24 h. In the in vitro study, Cou increased PG secretion in epithelial and stromal cells (P < 0.05). In both types of endometrial cells, Cou up-regulated PTGS-2 protein expression (P < 0.05). Moreover, PGES and PGFS proteins were up-regulated by Cou in epithelial cells (P < 0.01). These results indicate that Cou can disturb reproductive function by affecting reproductive hormone secretion and altering the endometrial milieu through PG stimulation. Coumestrol therefore may impair physiologic regulation of the estrous cycle and early pregnancy.

The combined effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and the phytoestrogen genistein on steroid hormone secretion, AhR and ERß expression and the incidence of apoptosis in granulosa cells of medium porcine follicles.

Low doses of endocrine disrupting chemicals (EDCs) used in combination may act in a manner different from that of individual compounds. The objective of the study was to examine in vitro effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 100 pM) and genistein (500 nM) on: 1) progesterone (P4) and estradiol (E2) secretion (48 h); 2) dynamic changes in aryl hydrocarbon receptor (AhR) mRNA and protein expression (1, 3, 6, 24 and 48 h); 3) dynamic changes in estrogen receptor ß (ERß) mRNA and protein expression (1, 3, 6, 24 and 48 h); and 4) induction of apoptosis in porcine granulosa cells derived from medium follicles (3, 6 and 24 h). TCDD had no effect on P4 or E2 production, but potentiated the inhibitory effect of genistein on P4 production. In contrast to the individual treatments which did not produce any effects, TCDD and genistein administered together decreased ERß and AhR protein expression in granulosa cells. Moreover, the inhibitory effect of TCDD on AhR mRNA expression was abolished by genistein. The treatments did not induce apoptosis in the cells. In summary, combined effects of low concentrations of TCDD and genistein on follicular function of pigs differed from that of individual compounds. The results presented in the current paper clearly indicate that effects exerted by low doses of EDCs applied in combination must be taken into consideration when studying potential risk effects of EDCs on biological processes.

Complications of percutaneous thrombin injection in patients with postcatheterization femoral pseudoaneurysm.

PURPOSE: To study the complications of ultrasound-guided thrombin injection of pseudo-aneurysms occurring after interventional cardiovascular procedures. METHOD: We prospectively studied 353 patients who developed post-catheterization femoral artery pseudo-aneurysms and were treated with ultrasound-guided thrombin injection. RESULTS: Arterial micro-embolization occurred in 53 patients (15%) and pulmonary embolism in 1 patient (0.3%). None of the patients developed significant peripheral arterial embolism. The length of the communicating channel between the arterial lumen and the pseudo-aneurysm was inversely correlated with the risk of embolization (p < 0.0001). A 4.6 mm increase in channel length decreased the odds of embolization by 14%, and patients with a channel less than 2 mm long were at greater risk. Repeated thrombin injection also increased the risk of embolization (p = 0.02). CONCLUSION: Thrombin injection for the treatment of post-catheterization femoral pseudo-aneurysm is feasible and safe, but it must be performed with caution, especially when the sac is directly communicating with the artery, or when success cannot be achieved with a single injection.

[Modern pharmacotherapy in heart failure with reduced ejection fraction: is further improvement in prognosis possible?].

A growing number of patients with chronic heart failure (CHF) is a combined result of aging and, paradoxically, the progress in management of cardiovascular diseases. The modern pharmacotherapy of HF with reduced ejection fraction (HFrEF) is based on the understanding of excessive neurohormonal activation as a key point in the pathophysiology and progression of HFrEF. The introduction of neurohormonal modifiers decreased significantly the mortality, survival and acute cardiac death rate. However, the rate of hospitalization increased and the quality of life is still poor. There is a large body of evidence on disease progression and mechanical heart failure as a main cause of death. The improvement in survival and decreasing the hospitalization rate remain a real challenge. The risk of death is the highest in the first weeks following hospitalization due to HF. The maintenance of stable patient condition is the priority of management. Pharmacotherapy at discharge should be optimized according to the prognostic factors to modify the clinical course of disease. Data from registries suggest that target doses are not reached and dose titration is not performed in outpatient clinics as it should be done according to guidelines. Taken together, the system of complex management of patients with HF focused on the management on discharge and early post-discharge period seems to be the best solution to identify the HF progression factors (suboptimal therapy, lack of revascularization, arrhythmia, concomitant diseases) and to improve the prognosis and the quality of life and to decrease the hospitalization rate.

[Risk factors and treatment of patients with ST-segment elevation myocardial infarction with cardiogenic shock].

Aim: To assess risk factors and prognosis in patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock (CS) in Poland. Methods: Data from The Polish Registry of Acute Coronary Syndromes (PL-ACS) were analysed in 2008-2012. A total of 57400 consecutive STEMI patients included. The results of treatment and prognosis of patients with and without CS were compared. An additional analysis of the prognosis of men and women with CS was performed. Results: There were 34.2% of women and 65.8% of men. CS was diagnosed in 3589 (6.3%) patients (females 7.3% vs. males 5.7%, p<0.003). In multivariate analysis CS was the strongest factor affecting both inhospital (OR 2.51; 95%CI 2.25-2.80; p<0.0001) and 12-month (OR 2.09; 95%CI 1.96-2.24; p<0.0001) mortality. The worst prognosis was associated with pulmonary edema, advanced age, left or right bundle branch block, atrial fibrillation, and anterior MI. An early invasive strategy up to six hours from the symptom onset were the only factors reducing in-hospital and 12-month mortality. Despite of high female ratio in the group with CS and higher mortality in the female group, the female sex did not influence the in-hospital prognosis. Conclusion: In spite of enormous progress in the treatment of STEMI cardiogenic shock remains an important complication affecting the in-hospital and long-term prognosis. A symptom onset-to-treatment time is the key element in the management of patients with CS. Proper diagnosis and management including wide interventional strategy implementation increase the survival chance. An intensive study on novel treatment modalities and on effective identification methods of patients at risk and are warranted.

Mechanisms of neutralization of a human anti-α-toxin antibody.

MEDI4893 is a neutralizing human monoclonal antibody that targets α-toxin (AT) and is currently undergoing evaluation in the field of Staphylococcus aureus-mediated diseases. We have solved the crystal structure of MEDI4893 Fab bound to monomeric AT at a resolution of 2.56 Å and further characterized its epitope using various engineered AT variants. We have found that MEDI4893 recognizes a novel epitope in the so-called "rim" domain of AT and exerts its neutralizing effect through a dual mechanism. In particular, MEDI4893 not only sterically blocks binding of AT to its cell receptor but also prevents it from adopting a lytic heptameric trans-membrane conformation.

Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections.

The Effects of Phytoestrogen Genistein on Steroidogenesis and Estrogen Receptor Expression in Porcine Granulosa Cells of Large Follicles.

Genistein is a biologically active isoflavone with estrogenic or antiestrogenic activity which can be found in a variety of soy products. Since in pigs' diet soy is the main source of protein, genistein may affect the reproductive/endocrine systems in these animals. Genistein has been shown to alter porcine ovarian and adrenal steroidogenesis but the mechanism of this action is still not clear. It is known that genistein binds to both estrogen receptor alpha (ERα) and estrogen receptor beta (ERß), although it has a higher affinity to ERß. Moreover, this phytoestrogen was demonstrated to posses the activity of protein tyrosine kinase (PTK) inhibitor. The aim of the study was to examine the in vitro effects of genistein on: (1) progesterone (P4) and estradiol (E2) secretion by porcine luteinized granulosa cells harvested from large follicles, and (2) the mRNA and protein expression of ERa and ERß in these cells. In addition, to verify the role of PTK-dependent mechanisms possibly involved in genistein biological action, we tested the effects of lavendustin C, the nonsteroidal PTK inhibitor, on granulosa cell steroidogenesis. Genistein significantly inhibited P4 and did not affect E2 secretion by porcine luteinized granulosa cells isolated from large follicles. Lavendustin C did not affect basal steroids secretion by examined cells. Genistein did not alter ERa but increased ERß mRNA levels in the cultured porcine granulosa cells. In contrast to medium follicles, the expression of ERß protein was unaffected by genistein in granulosa cells of large follicles. To conclude, the soy phytoestrogen genistein acts directly on the porcine ovary to decrease progesterone production and to increase the expression of ERß mRNA. Moreover, genistein-induced changes in follicular steroidogenesis and granulosal sensitivity to estrogens in pigs may depend on maturity of the follicles.

[Acute myocardia infarction associated with pregnancy]. / Zawal serca u kobiet w ciazy.

Pregnancy-associated myocardial infarction is rare but potentially fatal. Clinical course is different from nonpregnant patients. As it is predominantly non-atherosclerotic in origin, optimal treatment is not unequivocally established. Common anterior wall involvement results in developing of heart failure and its complications. There is a high risk of coronary artery dissection during percutaneous interventions. Pharmacological treatment, beneficial for mother, may be harmful for fetus. Long term prognosis is unclear.

[Non ST-segment elevation myocardial infarction in men and women with diabetes mellitus]. / Zawal serca bez uniesienia odcinka ST u kobiet i mezczyzn z cukrzyca.

BACKGROUND: Diabetes is a significant risk factor in patients with non ST-segment elevation myocardial infarction (NSTEMI). Sex-related differences in clinical course of NSTEMI have not been extensively studied. MATERIAL AND METHODS: During one year all consecutive patients presenting with NSTEMI and diabetes were enrolled. A total of 298 (158 women and 140 men) were analyzed. Clinical presentation, applied treatment and prognosis were compared between women and men. RESULTS: Women tended to be older. More men smoked cigarettes. Pharmacological approach was similar in both groups. Men underwent revascularization more often. Despite those differences both short- and long-term mortality were comparable. CONCLUSION: Despite the common knowledge on negative influence of diabetes and female sex in NSTEMI patients, in multivariate analysis only age and three or four Killip class on admission were significant.

[Influenza infection in intensive cardiac care unit patients]. / Infekcja wirusem grypy u pacjentów oddzialu intensywnej terapii kardiologicznej.

Infection with influenza type A virus may cause serious cardiovascular complications, such as myocarditis, heart failure, acute myocardial infarction. Also infection with influenza type AH1N1 may contribute to aggravation of cardiac disorders, i.e. acute coronary syndrome, heart failure, cardiogenic shock, severe ventricular arrythmias. One of the most fatal complication of influenza is pneumonia leading to acute respiratory insufficiency requiring artifitial ventilation. Symptoms of respiratory tract infections durnig influenza epidemy should always be treated with a high index of suspicion. Early diagnosis and adequate antiviral treatment may prevent those complications. A series of four cases of patients hospitalised in intensive cardiac care unit due to suspected cardiac dyspnea and finally diagnosed as a cardiac disease complicated by influenza pneumonia is presented.