Evaluation of serum heat shock protein 70 concentration in women with recurrent miscarriages

Background. Heat shock proteins (Hsp) were discovered over 50 years ago and are commonly called ‘stress proteins’. Hsp proteins play an important role in a cell, in that they provide protection against cellstress factors and environmentally negative factors. The most conservative, and the best known, heat shock proteins are Hsp 70 subfamily proteins. It has been suggested that an increase of Hsp 70 in the blood during pregnancy has a negative impact. The aetiology of recurrent miscarriages in more than 60% of women remains unexplained. Therefore the aim of this study was to evaluate the usefulness of Hsp 70 assessment in the diagnosis of recurrent miscarriages.Material and methods. The study group consisted of 100 women (aged 36.0 ± 4.9 years) who had experienced repeated miscarriages. The reference group consisted of 60 women (aged 36.1 ± 3.6 years), who had been pregnant at least twice and who had given birth by a spontaneous labour without complications. Hsp 70 was determined in the serum.Results. We found no significant differences in the Hsp 70 concentration between the women with recurrent miscarriages and the reference group. While median serum Hsp 70 was the most elevated in the women with the highest number of miscarriages, this difference was not significant.Conclusion. Based on the obtained results, it is difficult to determine whether Hsp 70 plays a causative role in recurrent miscarriages. However, taking into account the fact that the role of Hsp 70 in the course of normal and pathological pregnancy is not yet completely understood, it may be worth expanding the study to include a larger group of women with recurrent miscarriages

The assessment of usefulness of HE4 and CA125 quantification for the diagnostics of endometrial cancer

Endometrial cancer is one of the most prevalent uterine malignancies. This disease occurs mostly in older women, frequently affected with other comorbidities. Hence, it is important to search for novel, less burdensome diagnostic modalities, enabling the objective assessment of the patient’s status and facilitating qualification to relevant risk groups prior to surgical treatment.The aim of this study was to verify the usefulness of CA125 and HE4 in the evaluation of endometrial cancer.The study included 308 women treated at University Hospital No. 2 in Bydgoszcz. The study group included 180 patients operated due to endometrial cancer. The control group included 128 women operated due to perineal statics disorders. The concentrations of tumour markers were measured with ELISA-based ready-to-use diagnostic kits.Patients with endometrial cancer and healthy women differed significantly in terms of HE4 concentrations (P = 0.001). The serum concentration of HE4 in stage I endometrial cancer patients was significantly higher (Me = 88.37 pM) than in healthy women (Me = 46.14) (P = 0.007). The analysis of ROC curves with the determination of the area under curve showed 66.7% sensitivity and 78.1% specificity of HE4. AUC for HE4 amounted to 0.721 and was the highest of all markers.Our analysis revealed that HE4 is useful in the detection of endometrial cancer, while Human Epididymis Protein 4 can potentially be used for screening purposes. CA125 antigen, previously used in the diagnostic process, is useless or may possess limited usefulness. There is a need for further studies on larger populations of female patients

Mycophenolic Acid Metabolites Acyl-Glucuronide and Glucoside Affect the Occurrence of Infectious Complications and Bone Marrow Dysfunction in Liver Transplant Recipients.

BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis

Analysis of serum protein fractions from women with recurrent miscarriage

Recurrent miscarriage occurs in 1 - 5 % of women at reproductive age. The most common cause of recurrent miscarriage is chromosomal abnormalities of the embryo (41%), chromosomal aberrations parents (10%), anatomical abnormalities of the uterus (5%), infectious and hormonal factors. In about 25% of women, no cause of recurrent miscarriage is usually found. Therefore it seems important to study all factors possibly inducing pregnancy disorders. Objective: The aim of this study was to find a difference in serum protein fractions between women with primary and secondary recurrent miscarriage. Methods: The study group consisted of 52 women (aged 36.0±4.9) with recurrent miscarriage. Nine of them (17%) reported one earlier regular pregnancy ending with childbirth without complications. Control group comprised 30 non-pregnant women (aged 36.1±3.6), who had given vaginal birth to healthy children at least twice. Serum protein fractions were separated by electrophoresis in the SDS PAGE buffer system using a Mini PROTEAN 3 cell device. BioRad SDS PAGE Molecular Weight Standards covering mass range of 6.5-200 kDa were used as a reference. Gels were stained with Coomassie Blue R 250 solution. BioRad QuantityOne software was used for the assessment of molecular weight of each protein fraction. Results: Electrophoretic separation revealed 39 protein fractions of 10 243 kDa. Particularly interesting was a 38 kDa fraction present exclusively in serum of women with recurrent pregnancy, who had never given birth. Another fraction (74 kDa), not detected in the control group, was found in all women with recurrent pregnancy loss. Protein fractions of 76 and 151 kDa were present only in the control group. Conclusions: The presence of the protein fractions of low- or mid-weight in serum from women with recurrent miscarriage may potentially play a role in the pathomechanism of this disorder

The Role of Hypoxia-Inducible Factor-1α, Glucose Transporter-1, (GLUT-1) and Carbon Anhydrase IX in Endometrial Cancer Patients

Hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P=0.0115) were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P=0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) with a New Pathogenic Variant in TNFRSF1A Gene in a Family of the Adult Male with Renal AA Amyloidosis—Diagnostic and Therapeutic Challenge for Clinicians

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) belongs to systemic autoinflammatory diseases (AIDs). Many of these syndromes are genetically conditioned and can be inherited. Diagnosis relies on clinical symptoms and should be confirmed by genetic testing. One of the most serious complications is AA amyloidosis. We present the diagnostic route of a 33-year-old male with AA amyloidosis and his children, leading to diagnosis of monogenic autoinflammatory syndrome, confirmed by genetic analysis. A novel variant of the in-frame insertion type in one allele of TNFRSF1A gene was found by whole exome sequencing and confirmed by Sanger sequencing, which allowed a diagnosis of TRAPS. Three-dimensional modeling was used to assess the structural changes introduced into TNFR1 molecule by the insertion. The analysis of the 3D model revealed that accommodation of the 4AA insert induces misalignment of three cysteine bridges (especially the C70-C96 bridge) in the extracellular domain, leading to putatively misfolded and improperly functioning TNFR1. Three of the patient’s daughters inherited the same variant of the TNFRSF1A gene and presented TRAPS symptoms. TRAPS is a very rare disease, but in the presence of suggestive symptoms the genetic diagnostic workout should be undertaken. Early diagnosis followed by appropriate clinical management can prevent irreversible complications