Association of GPIa C807T polymorphism with unexplained female infertility and IVF implantation failure.

Glycoprotein Ia (GPIa), also known as integrin alpha 2 (ITGA2), together with GPIIa (ITGB1), form the heterodimer integrin α2ß1. This complex is a major collagen receptor on the membrane of platelets, which is involved in thrombus formation through platelet adhesion and activation.

Association of plasminogen activator inhibitor-type 1 (PAI-1) -675 4G/5G polymorphism with unexplained female infertility.

BACKGROUND: Infertility is a major issue of concern for couples at reproductive age.  The underlying causes of infertility remain unknown in 15-30 % of the cases. Plasminogen activator inhibitor type 1 (PAI-1), which is a major fibrinolytic factor, has been associated with increased infertility risk.  DNA variants at PAI-1, such as -675 4G/5G promoter polymorphism, have been implicated in infertility-related reproductive disorders, possibly due to a molecular mechanism involving implantation failure. This study aims to investigate the association of PAI-1 4G/5G polymorphism to otherwise unexplained female infertility in a sample of women of Greek ethnic origins. METHODS: We enrolled in this study 222 women from the population of Northern Greece; 115 women with unexplained infertility (group 1) and 107 normal fertile women (group 2). All participants were genotyped for PAI-1 -675 by real-time polymerase chain reaction. RESULTS: Our results indicate an association with the PAI-1 4G allele in our sample of women with unexplained infertility. The dominant genetic model supports the association, in contrast to the recessive genetic model. CONCLUSIONS: Our results indicate that PAI-1 4G/5G polymorphism is a promising screening factor which could potentially be a target for certain cases of unexplained female infertility. However, they should be interpreted with caution and should be validated in larger studies and diverse populations. In addition, other variants in genes involved in thrombophilia might need to be considered. HIPPOKRATIA 2017, 21(4): 180-185.

Treatment of a patient with classical paroxysmal nocturnal hemoglobinuria and Budd-Chiari syndrome, with complement inhibitor eculizumab: Case Report.

Background. Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired clonal disorder of hematopoietic stem cells involving all blood cells. Erythrocytes have increased susceptibility to complement-mediated haemolysis. Thrombosis is the leading cause of mortality and follows episodes of acute hemolysis. Eculizumab, a monoclonal antibody blocking activation of complement C5 is currently used in the treatment of PNH. Recent results demonstrated that eculizumab effectively reduces thrombosis. Description of case. We present a 30-year-old male patient admitted with abdominal and lumbar pain. Thorough investigation revealed severe hemolytic anemia requiring transfusions and hepatosplenomegaly. Imaging findings were compatible with a Budd-Chiari syndrome. Flow cytometry confirmed the PNH diagnosis. Due to refractory ascites he underwent a transjugular intrahepatic portal-systemic shunt (TIPS) and eculizumab administration was started. Results. He has already completed three years of eculizumab treatment and he is transfusion independent. There is also a significant reduction in fatigue with improvement in his quality of life. Doppler scans of his TIPS persistently show it to be patent. Conclusions. Classical PNH patients with thrombosis and severe intravascular hemolysis are particularly challenging to manage. For these patients, eculizumab is a reasonable therapeutic option, expecting that by decreasing the risk for thrombosis, life expectancy may be increased.

Prevalence of thrombophilic mutations in patients with unprovoked thromboembolic disease. A comparative analysis regarding arterial and venous disease.

BACKGROUND: Thromboembolic disease (TED) represents one of the main reasons of morbitity and mortality in Western World. Venous and arterial thrombotic disorders have long been viewed as separate pathophysiological entities. However, in recent times the separate nature of arterial and venous thrombotic events has been challenged. Although inherited thrombophilia's predominant clinical manifestation is venous thrombosis, its contribution to arterial thrombosis remains controversial. Purpose  of  the  study  was  to  evaluate  the  prevalence  of  the  most common  thrombophilic  mutations, FV Leiden G1691A-FVL and FII G20210A-PTM and to assess  the  differences between venous, arterial and mixed thrombotic events. Testing  for polymorphism MTHFR C677T and  antithrombin,  protein  C  and  protein  S was also performed. Correlations with  dyslipidemia, smoking, obesity, homocysteine and antiphospholipid antibodies were made. METHODS: 515 patients with unprovoked TED, 263 males, median age 44 years, were studied. Patients were divided into three groups: 258 with venous thrombosis (group A), 239 with arterial (group B) and 18 with mixed episodes (group C). All patients were interviewed regarding family history of TED, origin, smoking and dyslipidemia. Body mass index (BMI) had been calculated. Molecular assessment of the FVL, PTM and MTHFR C677T was performed. Antithrombin, protein C, protein S, APCR, homocysteine, antiphospholipid antibodies and lipid profile were also measured. RESULTS: The population studied was homogenous among three groups as regards age (p=0.943), lipid profile (p=0.271), BMI (p=0.506), homocysteine (p=0.177), antiphospholipid antibodies (p=0.576), and positive family history (p=0.099). There was no difference in the prevalence of FVL between venous and arterial disease (p=0.440). Significant correlation of PTM with venous TED was found (p=0.001). The number of positive and negative for MTHFR presented statistically significant difference with a support in arterial disease (p=0.05). Moreover, a 2-fold increase in the risk of venous thrombosis in FVL positive patients (odds ratio: 2.153) and a positive correlation of homocysteine levels with MTHFR C677T (p<0.001) was found. CONCLUSIONS: Correlation of PTM with venous thrombosis was established. Analysis showed no difference in prevalence of FVL between venous and arterial thrombosis, indicating that FVL might be a predisposing factor for arterial disease. A significant increase in MTHFR C677T prevalence in arterial disease was found. In conclusion, young patients with unprovoked arterial disease should undergo evaluation for thrombophilic genes. Identification of these mutations is important in the overall assessment and management of patients at high risk. Findings will influence the decisions of stratified approaches for antithrombotic therapy either primary or secondary thromboprophylaxis, the duration of therapy, the potential for avoiding clinical thrombosis by risk factor modification and the genetic counselling of family members. However, further studies are needed to clarify the nature of the association regarding venous and arterial thrombotic events.

Acute renal dysfunction in a patient presenting with rhabdomyolysis due to Hypothyroidism attributed to Hashimoto's Disease.

We describe a patient with rhabdomyolysis and acute renal dysfunction due to hypothyroidism, attributed to Hashimoto's disease. Though rhabdomyolysis could be life-threatening, it is a rare complication of hypothyroidism, especially when other precipitating factors, such as exercise, alcohol, medications or renal failure, are absent. Nevertheless, hypothyroidism can be an authentic cause of rhabdomyolysis and should always be considered when elevated creatine kinase (CK) and other muscle enzymes concentrations cannot be attributed to any major factor.

Normal peak nasal inspiratory flow rate values in Greek children and adolescents.

BACKGROUND AND AIM: Peak Nasal Inspiratory Flow Rate (PNIFR) is a clinical trial that has been instituted in clinical practice in order to determine the extent of nasal airway patency and it is used to assess the degree of nasal obstruction. This study attempts to provide tables referring to normal values of PNIFR in children and adolescents. PATIENTS AND METHODS: Three thousand one hundred and seventy pupils aged between 5-18 years, were selected to enter the study. Children with acute or chronic upper airway obstruction, such as acute obstructive pulmonary disease or allergic rhinitis and children below the 3rd percentile for weight and/or height were excluded from the study. All children that took part in the study were subjected to PNIFR measurements by using a portable Youlten Peak Flow meter. RESULTS: A continuous increase of PNIFR values for boys and girls in relation to age increase was recorded. PNIFR values were higher in boys compared to girls and this difference was statistically significant until the age of 12. CONCLUSION: Normal ranges for PNIFR standards are of great importance for the study of nasal patency, evaluation of the degree of nasal obstruction and application of treatment. This is the first time that a detailed description of PNIFR standards becomes available for the Greek population of children and adolescents.

Contributions of signal analysis to the interpretation of spirometry.

AIM: Chronic Obstructive Pulmonary Disease (COPD) is taking on catastrophic proportions. However, there is still a need for more objective and quantitative methods for its diagnosis and stratification. The present study explores the effectiveness of signal analysis methodologies as the means to increase the effectiveness of spirometry in diagnosing and stratifying COPD. METHODS: Since expiratory flow at the mouth results from converging airflows, it is possible to use signal analysis to identify changes in the characteristics of airflow along the respiratory tree. This was achieved by non-invasively identifying alterations in the frequency spectrum of the Forced Expiratory Flow (FEF) curve of 108 patients (49 men and 59 women, 12-75 yrs of age) presenting with (a) clinically and spirometrically normal respiratory profile, (b) COPD, (c) restrictive lung disease and (d) interstitial fibrosis. Fundamental to the study design was the notion that the characteristics of the expiratory output of the respiratory system are determined by the bronchial tree and the upper respiratory tract. RESULTS: A number of quantitative measures for the power spectrum of the FEF curve were identified, which permit the definition of specific rules and allow for the accurate classification of, at least, the basic types of respiratory disease. CONCLUSIONS: (a) It is for the first time that airflow resonances are identified in the sub-audible (<20 Hz) range of the power spectrum of the FEF curve. (b) COPD patients present with FEF curves which have different power spectral characteristics from those of healthy individuals (p<0.01), at frequencies lower than 3.66 Hz. (c) In COPD, in restrictive lung disease and in interstitial fibrosis, the lower resonant frequencies of the spectrum of the FEF curve predominate.

The proteins and the mechanisms of apoptosis: a mini-review of the fundamentals.

Apoptosis or programmed cell death is a physiological mechanism, characterized by specific morphological and biochemical changes such as cell shrinkage, chromatin condensation, protein cleavage, DNA breakdown and phagocytosis. Apoptosis is a significant contributor to the morphologic and functional development of multicellular organisms. It is also involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS) like Alzheimer's disease or Parkinson's disease, cancer and immune system dysfunction. There are many factors, mainly proteins, which are involved in the activation, regulation and execution of related events. A fairly detailed outline of apoptotic mechanisms has also started to emerge and to be verified. In this short, focused mini-review, we attempt to outline current evidence regarding the mechanisms and the regulation of apoptosis.

Interleukin -1beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor (TNF) in plasma and pleural fluid of pneumonia, lung cancer and tuberculous pleuritis.

Interleukins IL-1beta, IL-6 and TNF are increased in plasma of patients with severe infections and septic shock. Our objective was the evaluation of IL-1beta, IL-6 and TNF in plasma and exudates of pleural fluid and their contribution to the diagnosis. We studied 44 patients, 27 men and 17 women with mean age 66.81 +/- 11.75 years; 16 with pneumonia and parapneumonic effusion, 14 with primary lung cancer and pleural effusion and 14 with tuberculous pleuritis. We measured IL-1beta, IL-6 and TNF in serum and pleural fluid with ELISA. In patients with pneumonia and parapneumonic effusion the mean value of IL-1beta IL-6 and TNF in plasma was 9.05, 19.24 and 21.34 pg/ml and in pleural fluid 10.34, 32.19 and 25.30 pg/ml. In patients with lung cancer the mean values of IL-1beta, IL-6 and TNF were 5.33, 11.74 and 11.51 pg/ml and 6.70, 13.13, 20.89 pg/ml, respectively. In those with tuberculous pleuritis the respective mean values were 10.33, 49.94, 21.27 pg/ml and 14, 56.59, 23.58 pg/ml. In conclusion, IL-1beta and IL-6 were found increased in plasma and tuberculous pleural fluid, indicating an inflammatory status.

A case of pleurisy associated with antibodies to Rickettsia conorii.

Rickettsia conorii is endemic in Mediterranean area. We describe an unusual sace of R. Conorii infection, which concerns a farmer with clinical, radiological and cytological findings of pleurisy without evidence of malignancy. An elevated antibody titre for R. Conorii was observed, using an indirect immunofluorescent antibody test. After treatment with Doxycycline, the patient presented a significant improvement of his clinical and radiological image and a four-fold decrease of the antibody titre for R. conorii.

The effect of loratadine on activated cells of the nasal mucosa in patients with allergic rhinitis.

The effect of loratadine on the numbers of activated cells--cells expressing interleukin-2 receptors(IL-2R), HLA-DR antigens and proliferating cell nuclear antigen (PCNA)--in the nasal mucosa was studied in 48 patients with allergic rhinitis. Patients were treated with either loratadine (10 mg) or placebo for 1 month. At the end of treatment, a significant decrease in the symptom scores was noted in both groups of patients. However, the clinical score was significantly lower in the loratadine group compared to the placebo group. At the end of treatment, the numbers of IL-2R+, HLA-DR+ and PCNA+ cells were significantly decreased only in the group on loratadine. An almost significant correlation was also observed between the numbers of IL-2R+ cells and symptoms in the loratadine group. Our results show that loratadine exerts its beneficial effect possibly by inhibiting both the action of histamine and immune activation.

Effect of salbutamol, ipratropium bromide and cromolyn sodium on prostaglandin F2 alpha-induced bronchospasm.

We studied the effects of salbutamol, ipratropium bromide and cromolyn sodium on PGF2 alpha-induced bronchospasm in ten patients with asthma. Initially, the bronchial reactivity to IC-PGF2 alpha and the DP20-PGF2 alpha were determined. Recalculations were made two days later and again 1 h after administration of various drugs given on different days. Salbutamol and ipratropium bromide induced significant bronchodilation and of similar magnitude 1 h after administration. On the day salbutamol was given, surface area under the dose-response curve to PGF2 alpha was significantly higher and the final drop of FEV1 significantly lower than those observed on days when placebo, ipratropium bromide and cromolyn sodium were given. No differences among these values were found for placebo, ipratropium bromide and cromolyn sodium. Thus, beta 2 stimulants attenuate significantly PGF2 alpha-induced bronchospasm, while ipratropium bromide and cromolyn sodium do not have protective effect.