Benzpyrene exposure at 15 days of prenatal life reduces the binding capacity of thymic glucocorticoid receptors in adulthood.

1. The offspring of female rats treated with a single dose of benzpyrene on day 15 of gestation showed in adulthood a significant relative decrease in the number of thymic glucocorticoid receptors, without an appreciable decrease in binding affinity. 2. There is experimental evidence that exposure to a hormone analogue in the early stage of organogenesis effects receptor development and the maternal organism fails to confer protection against that untoward influence.     

Lasting impact of a single benzpyrene treatment in pre-natal and growing age on the thymic glucocorticoid receptors of rats.

1. Rats exposed to benzpyrene in utero at 19 days of pre-natal life showed a relative decrease in the number of thymic glucocorticoid receptors at 6 weeks of age. 2. Primary exposure to benzpyrene at 6 weeks of age had a similar effect on females 4 weeks later, but did not change the glucocorticoid receptor number of males. 3. In utero exposure accounted for an increase in the fetal cytochrome P450 level within 1 day, whereas exposure at 6 weeks of age did not change it within 4 weeks. 4. It appears that exposure to benzpyrene gives rise to a faulty imprinting of the thymic glucocorticoid receptor in both fetal and growing age, to judge from a lasting change in the receptor number.     

Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery

BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.     

Case of Pediatric Bullous Systemic Lupus Erythematosus Treated with Intravenous Immunoglobulin

This is a case report of a 16‐year‐old girl recently diagnosed with systemic lupus erythematosus (SLE) who presented with multiple blisters on the face, hands, arms, legs, trunk, and vaginal and oral mucosa. Skin biopsy was consistent with bullous SLE (BSLE). Dapsone is often the first‐line treatment option for BSLE, but the patient's history of anemia and leukopenia and long‐term immunosuppression requirement for her systemic symptoms raised concerns about dapsone and bone marrow toxicity, especially hemolytic anemia and agranulocytosis. She was started on intravenous immunoglobulin (IVIG), 2 g/kg divided over 3 days, with significant improvement in her cutaneous symptoms. IVIG is a treatment option for BSLE patients in whom agents such as dapsone are contraindicated.     

An entropy spring model for the Young’s modulus change of biodegradable polymers during biodegradation

This paper presents a model for the change in Young’s modulus of biodegradable polymers due to hydrolysis cleavage of the polymer chains. The model is based on the entropy spring theory for amorphous polymers. It is assumed that isolated polymer chain cleavage and very short polymer chains do not affect the entropy change in a linear biodegradable polymer during its deformation. It is then possible to relate the Young’s modulus to the average molecular weight in a computer simulated hydrolysis process of polymer chain sessions. The experimental data obtained by Tsuji [Tsuji, H., 2002. Autocatalytic hydrolysis of amorphous-made polylactides: Effects of L-lactide content, tacticity, and enantiomeric polymer blending. Polymers 43, 1789–1796] for poly(L-lactic acid) and poly(D-lactic acid) are examined using the model. It is shown that the model can provide a common thread through Tsuji’s experimental data. A further numerical case study demonstrates that the Young’s modulus obtained using very thin samples, such as those obtained by Tsuji, cannot be directly used to calculate the load carried by a device made of the same polymer but of various thicknesses. This is because the Young’s modulus varies significantly in a biodegradable device due to the heterogeneous nature of the hydrolysis reaction. The governing equations for biodegradation and the relation between the Young’s modulus and average molecular weight can be combined to calculate the load transfer from a degrading device to a healing bone.     

Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats

Aging is associated with a gradual decline in cognitive and motor functions, the result of complex biochemical processes including pre- and posttranslational modifications of proteins. Sirtuins are NAD⁺ dependent protein deacetylases. These enzymes modulate the aging process by lysine deacetylation, which alters the activity and stability of proteins. Exercise can increase mean life-span and improve quality of life. Data from our laboratories revealed that 4 weeks of treadmill running improves performance in the Morris Maze test for young (4 months, old) but not old (30 months, old) male rats, and the exercise could not prevent the age-associated loss in muscle strength assessed by a gripping test. The positive correlation between protein acetylation and the gripping test suggests that the age-dependent decrease in relative activity of SIRT1 in the cerebellum impairs motor function. Similarly to the acetylation level of total proteins, the acetylation of ά -tubulin is also increased with aging, while the effect of exercise training was not found to be significant. Moreover, the protein content of nicotinamide phosphoribosyltransferase, one of the key enzymes of NAD biosynthesis, decreased in the young exercise group. These data suggest that aging results in decreased specific activity of SIRT1 in cerebellum, which could lead to increased acetylation of protein residues, including ά-tubulin, that interfere with motor function.     

Familiar ochronotic arthropathy–caused by a gene mutation traced three hundred years

Authors trace an ochronotic Hungarian family, which moved from Slovakia to Hungary 300 years ago. As the family members lived in a relatively close village community the gene mutation had been survived silently for ages before the clinical symptoms developed. Family tree analysis could detect with the use of allele specific PCR amplification–the p.G161R mutation of the homogentisic acid 1,2-dioxygenase (HGD) gene, which resulted in a specific genotype appearing in the Slovak population. We found a heterozygote member of this family who has children with an alkaptonuria-homozygote and known–heterozygote genotypes so there would be a high risk of alkaptonuria in their offsprings. Therefore genetic counselling is highly recommended to minimize the risk factors.     

A possible explanation of the germicide effect of carbon dioxide in supercritical state based on molecular-biological evidence

Supercritical carbon dioxide (CO₂) possesses germicide (bactericide and sporicide) effect. Despite of the fact, that this effect is used in industrial sterilization processes, the sterilization mechanism at molecular level is unclear. Our hypotheses can provide a molecular-biological explanation for the phenomenon.     

Effect of perinatal stress on the biogenic amine neurotransmitter level of the adult rat's brain

The amount of biogenic amines (dopamine and serotonin) and their metabolites (DOPAC, HVA, 5-HIAA, and 5-HTOL) in five regions of the brain (frontal cortex, hypothalamus, hippocampus, striatum, and brainstem) was studied in the male and female offspring of control and perinatally (48 h before birth or 48 h after birth) food and water deprived dams, when they were three months old, by using HPLC-EC determination. The increase of amine or metabolite level was dominant (19 values increased and 10 decreased related to control). Before-birth stress caused increase in 9 case and only 2 decreased, while in the case of after-birth stress 10 increased and 8 decreased. However, though there is no possibility to decide an exact tendency of direction, the after-birth stress (transmitted by milk) has more expressed effect. Striatum and brainstem were the most touched regions. There was a gender dependence with the dominance of males, except striatum. Blood plasma nociceptin level was also studied and there was a significant elevation in males after pre- and postnatal deprivation, while in females only after postnatal deprivation. The importance of the results in correlation with other stress effects is discussed.     

Beta lactoglobulin homologue placental protein 14 (PP14) in serum of patients with trophoblastic disease and non-trophoblastic gynecologic malignancy

Summary Serum levels of beta lactoglobulin homologue placental protein 14 (PP14) were measured by a sensitive radioimmunoassay in various trophoblastic diseases and non-trophoblastic gynecologic malignancies. While trace amounts of protein were detected in sera of non-pregnant subjects (22.3±13.7 g/l), during first half of normal pregnancy a dramatic rise of serum-PP14 levels was demonstrable with a peak-value at 7th–10th week of gestation, followed by a decline thereafter. Serial determinations of PP14 have been performed in 31 patients with trophoblastic tumour (20 hydatidiform moles, 4 invasive moles and 7 choriocarcinomas). In patients with hydatidiform moles and invasive moles (273.5±106.5g/l and 162.2±109.6g/l) respective values before therapy were much exceeding the nonpregnant controls. After therapy there was a rapid decline of the serum-PP14 levels within two weeks. In patients with choriocarcinoma the PP14 values were moderately elevated (66.4±25.7g/l), and declined following the remission of disease. In 32 gynecological tumours (21 carcinomas of the cervix, 4 endometrial carcinomas, 5 ovarian carcinomas, 2 carcinomas of the vulva) the pretreatment levels were not different to normal controls.