The influence of caffeine on the biomechanical properties of bone tissue during pregnancy in a population of rats

The influence of pregnancy on bone tissue metabolism is not completely understood. Caffeine also has a potentially negative influence on bones. The aim of this study was the evaluation of changes in the bones of pregnant rats under the influence of caffeine. The experiment was carried out on Wistar rats. The evaluation of rats' bone tissue quality was performed based on bone density measurements and resistance examinations. It analyzed the impact of caffeine on the degree of bone tissue mineralization and the composition of the bones. The mean value of pelvises 'wet' and 'dry' densities in a group of pregnant rats with caffeine intake was lower compared to the control group. The deformation in maximal load point of the femur shaft in the experimental group was significantly higher than in the control group. In the experimental group, the percentage of water in the bones was significantly higher, while the content of inorganic phase was significantly lower compared to the control group. The changes of biomechanical parameters in the group of pregnant rats with caffeine intake indicate its negative influence on the bone. Our results show higher plasticization of the bone shafts of the animals under the influence of caffeine. Higher deformation of bone shafts may have an effect on the statics of the skeleton. The administration of caffeine significantly affected the quantitative composition of the bone.     

Enhanced expression of Fas Ligand (FasL) in the lower airways of patients with fibrotic interstitial lung diseases (ILDs)

The exact role of FasL, and particularly its soluble and membrane-bound forms, in the development of chronic ILDs and lung fibrosis has not been extensively explored. We aimed at analyzing membrane-bound FasL expression on alveolar macrophages (AM) and lymphocytes (AL) as well as soluble FasL (sFasL) levels in bronchoalveolar lavage (BAL) from ILDs patients, incl. pulmonary sarcoidosis (PS), hypersensitivity pneumonitis (HP), silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and healthy subjects (n = 89, 12, 7, 8, 23, 6, 17, respectively). In IPF, significantly increased percentage of AM FasL(+) and CD8(+)FasL(+) cells as well as sFasL levels in BAL were found. Increased sFasL levels were also observed in HP. NSIP and asbestosis were characterized by higher AM FasL(+) relative number; CD8(+)FasL(+) population was expanded in asbestosis only. There was a significant decline in AL FasL(+) percentage in PS and HP. Vital capacity was negatively correlated with sFasL levels, AM FasL(+) and CD8(+)FasL(+) cell relative count. CD4(+)FasL(+) and CD8(+)FasL(+) percentage strongly correlated with BAL neutrophilia, an unfavorable prognostic factor in lung fibrosis. The concurrent comparative BAL analysis of FasL expression indicates that FasL(+) AM and AL (mainly Tc cells) comprise an important element of the fibrotic process, mostly in IPF. FasL might play a crucial role in other fibrosis-complicated ILDs, like NSIP and asbestosis.     

Cathepsin E (EC 3.4.23.34)--a review

Cathepsin E belongs to the third class of enzymes - hydrolases, a subclass of peptide bond hydrolases and a sub-subclass of endopeptidases with aspartic catalytic sites. Cathepsin E is an endopeptidase with substrate specificity similar to that of cathepsin D. In a human organism, cathepsin E occurs in: erythrocytes, thymus, dendritic cells, epithelial M cells, microglia cells, Langerhans cells, lymphocytes, epithelium of gastrointestinal tract, urinary bladder, lungs, osteoclasts, spleen and lymphatic nodes. In human cells, loci of the gene of pre-procathepsin E are located on chromosome 1 in the region 1231-32. The catalytic site of cathepsin E is two residues of aspartic acid - Asp96 and Asn281, occurring in amino acid triads with sequences DTG96-98 and DTG281-283. To date, no particular role of cathepsin E in the metabolism of proteins in normal tissues has been found. However, it is known that there are many documented pathological conditions in which overexpression of cathepsin E occurs.     

An association between DNA repair gene polymorphisms and survival in patients with resected non-small cell lung cancer

DNA repair genetic polymorphisms have been studied extensively in relation to lung cancer susceptibility, but much less is known about their role in clinical outcome modulation. In this report, we examined effect of the XPA −4G>A, XPD Asp312Asn, Leu751Gln, hHR23B Ala249Val, XPG Asp1104His, XRCC1 Arg399Gln, XRCC2 −4234G>C and XRCC3 Thr241Met polymorphisms on overall survival in 162 patients with resected non-small cell lung cancer (NSCLC). The XRCC3 Met/Met genotype was significantly associated with increased risk of death among all patients and men in uni- and multivariate analyses. The risk was higher for adenocarcinoma patients possessing the XRCC3 Met/Met or XRCC1 Gln/Gln genotypes, although their frequency was small. The XRCC1 399Gln allele was also associated with poor prognosis in stage II–IIIA and among older individuals. Men homozygous for the XPD 312 Asn/Asn had significantly better survival with the risk of death being at borderline significance in uni- and multivariate models. Younger cases and ever smokers smoking less than median pack-years showed significantly increased risk of death associated with the XPA −4A allele. A presence of one or two XRCC2 −4234C alleles had a protective effect in males and ever smokers with lower cumulative smoking dose, although the CC genotype was rarely observed. When number of combined risk alleles was considered, we found that carriers of >4 adverse alleles were at significantly increased risk of death in uni- and multivariate models. Therefore, our results indicate that selected genetic polymorphisms in DNA repair genes may influence overall survival in resected NSCLC.     

DNA intercalation without flipping in the specific ThaI–DNA complex

The PD-(D/E)XK type II restriction endonuclease ThaI cuts the target sequence CG/CG with blunt ends. Here, we report the 1.3 Å resolution structure of the enzyme in complex with substrate DNA and a sodium or calcium ion taking the place of a catalytic magnesium ion. The structure identifies Glu54, Asp82 and Lys93 as the active site residues. This agrees with earlier bioinformatic predictions and implies that the PD and (D/E)XK motifs in the sequence are incidental. DNA recognition is very unusual: the two Met47 residues of the ThaI dimer intercalate symmetrically into the CG steps of the target sequence. They approach the DNA from the minor groove side and penetrate the base stack entirely. The DNA accommodates the intercalating residues without nucleotide flipping by a doubling of the CG step rise to twice its usual value, which is accompanied by drastic unwinding. Displacement of the Met47 side chains from the base pair midlines toward the downstream CG steps leads to large and compensating tilts of the first and second CG steps. DNA intercalation by ThaI is unlike intercalation by HincII, HinP1I or proteins that bend or repair DNA.     

Management of thyroid diseases during pregnancy

The management of thyroid disorders during pregnancy is one of the most frequently disputed problems in modern endocrinology. It is widely known that thyroid dysfunction may result in subfertility, and, if inadequately treated during pregnancy, may cause obstetrical complications and influence fetal development. The 2007 Endocrine Society Practice Guideline endorsed with the participation of the Latino America Thyroid Association, the American Thyroid Association, the Asia and Oceania Thyroid Association and the European Thyroid Association, greatly contributed towards uniformity of the management of thyroid disorders during pregnancy and postpartum. Despite the tremendous progress in knowledge on the mutual influence of pregnancy and thyroid in health and disease, there are still important areas of uncertainty. There have been at least a few important studies published in the last 3 years, which influenced the thyroidal care of the expecting mother. It should also be remembered that guidelines may not always be universally applied in all populations with different ethnical, socio-economical, nutritional (including iodine intake) background or exposed to different iodine prophylaxis models. The Task Force for development of guidelines for thyroid dysfunction management in pregnant women was established in 2008. The expert group has recognized the following tasks: development of the coherent model of the management of thyroid dysfunction in pregnant women, identification of the group of women at risk of thyroid dysfunction, who may require endocrine care in the preconception period, during pregnancy and postpartum - that is in other words, the development of Polish recommendations for targeted thyroid disorder case finding during pregnancy, and the development of Polish trimester-specific reference values of thyroid hormones. Comprehensive Polish guidelines developed by the Task Force are to systematize the management of the thyroid disorders in pregnant women in Poland.     

A case of Cushing's syndrome in pregnancy

Cushing's syndrome (also known as hypercortisolemia) is rare in pregnant women due to the menstrual disturbances and infertility in women with hypercortisolism. A diagnosis of pathological hypercortisolism in pregnant women is often difficult as some symptoms of the disease may be associated with a complicated pregnancy. Hypercortisolemia leads to serious complications for mother and foetus, and is associated with premature labour and high foetal mortality. Hormonal and radiological diagnostics in pregnancy are limited. The results of hormonal measurements and dynamic tests are difficult to interpret due to the physiological changes in the hypothalamo-pituitaryadrenal axis connected with pregnancy. The optimal time and method of treatment should be chosen cautiously case by case because of the possibility of maternal and foetal complications. In this paper, we present a case of Cushing's syndrome secondary to adrenal adenoma in which the diagnosis was made in the 22(nd) week of pregnancy. Due to the advanced gestational status and mild symptoms of hypercortisolism, only symptomatic treatment was introduced. The patient was under continuous obstetric and endocrinological care. At 35 weeks of gestation, the pregnancy was terminated by emergency caesarean section because of premature detachment of the placenta. A male infant weighing 2,450 g was delivered; neither adrenal insufficiency in the child nor hypercortisolemia complications in the mother were observed.