Aging, hormones and receptors.

Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In particular, we focused on the changes associated with aging, especially the role of small molecules, their role in physiological and pathophysiological processes and potential treatment options. Our previously published results and data from other authors lead to the conclusion that these unwanted changes are mainly linked to the hypothalamic-pituitary-adrenal axis can be slowed down, stopped, or in some cases even reversed by an appropriate treatment, but especially by a life-management adjustment.

Physiological changes after spa treatment - a focus on endocrinology.

The paper presents the results of our effort to reveal objective parameters for evaluation of the spa treatment for patients with anxiety-depressive disorders. The study was based on our previous experience with neuroactive steroids and neurosteroids, which play a crucial role in the psychological well-being of patients by maintaining balance of the organism. A total number of 94 steroids were determinated in a group of 70 female patients diagnosed with anxiety-depressive disorders. Patients underwent a month spa treatment while maintaining unchanged medication dosing with SSRI (selective serotonin reuptake inhibitors). The other investigated factors contributing to improving the health of treated subjects were amino-acid homocysteine and serotonin. The blood samples were collected at the beginning and the end of the spa treatment. Serotonin in all patients increased by a relative 23 % (results given as relative differences in percent), while homocysteine decreased by 17.1 %. Statistically significant increases were found in 21 steroids, which indicate activation of the adrenal cortex. It can be assumed, that the overall improvement in the mental condition of patients, which was proved by questionnaire from Knobloch and Hausner, the increase in immune suppressive substances and anti-autoimmune responses, will maintain for a longer time after the spa treatment.

[Analysis of 6,879 groin hernia surgeries in the Czech Republic using data from a health insurance company]. / Analýza 6879 operací tríselné kýly v Ceské republice z pohledu databáze Vojenské zdravotnípojistovny Ceské republiky.

INTRODUCTION: Information about actual results of provided surgical care is difficult to obtain. We tested the insurance company billing system in terms of data usability. METHODS: 6,879 groin hernia surgeries carried out from 2008 to 2015 were analysed using registry data of one health insurance company. RESULTS: Groin hernia surgeries were performed by 156 providers in the Czech Republic. Day surgeries were used in 3.8% cases (248), of which laparoscopic surgeries were used in 77% (193) of patients. The other 96.2% (6,631) surgeries were carried out on inpatients with the median hospital stay of 4 days. Of this number: open procedures without the use of a mesh were done in 36.54% (2,423), open procedures using a mesh in 19.84% (1,316), and laparoscopic procedures in 43.61% (2,892) cases. Reoperations for recurrence after hernia repair were done in 1.85% (127) of all cases, while 2.76% (66) reoperations were done after open procedures without the use of a mesh, 1.66% (22) after open procedures using a mesh, and 1.19% (37) after laparoscopic surgeries. The prediction rate for recurrent hernia incidence within 5 years was 2.42% in all cases. Others parameters were also evaluated. CONCLUSION: The study confirmed usefulness of the DRG data registry of health insurance companies for obtaining relevant information on the surgical procedures. KEY WORDS: groin hernia - treatment - database - day surgery - health insurance company.

Health resort treatment improved the neurosteroid profile in thyroidectomized women.

OBJECTIVE: The aim was to study the effect of climatotherapy and spa treatment on selected neuro- and immunomodulatory steroids known to affect well-being, and homocysteine, in a homogenous group of thyroidectomized women under standard substitution regime. METHODS: Dehydroepiandrosterone, its precursors and metabolites, cortisol, major sex steroids, SHBG, and homocysteine were measured before and after three-weeks stay in a health resort Jeseník (Graefenberg) in Czech Republic. The studied group consisted of 21 women after total thyroidectomy which was performed at least 3 months before the admission to the spa resort. All patients received thyroid hormone substitution treatment which was not changed during their stay in that resort. RESULTS: Out of the steroids investigated, five, namely dehydroepiandrosterone, androstenedione, testosterone, 7beta-hydroxy-dehydroepiandrosterone and cortisol were changed significantly after treatment. The most considerable was the decrease of cortisol and of homocysteine (p < 0.000 each). CONCLUSION: Spa resort treatment of thyroidectomized women substituted with thyroid hormones resulted in significant, mostly beneficial effects on steroid spectrum. This effect was achieved without any use of psychopharmacs.

Thermal, cardiac and adrenergic responses to repeated local cooling.

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.

Granulocytic protein p25 is a DNA-binding subunit of protein M(r) = 50,000: subcellular localization, cell and species specificity.

We have previously reported the presence and isolation of the novel protein M(r) = 25,000 (p25) from human granulocytes. In this study, the protein p25 was characterized by its: (a) ability to bind DNA, (b) subunit association, (c) partial protein sequencing, (d) subcellular localization, (e) cellular and species specificity and (f) stability in the presence of released granulocytic proteinases. For the detection of p25 in various extracts, fractions and types of human or animal hematopoietic cells, SDS-PAGE/Western blotting and immunohistochemical staining were used. The protein p25 was subjected to N-terminal amino acid sequence analysis. Protein p25-DNA interactions were monitored using Southwestern blotting. Selective inhibition of granulocytic proteinases was performed. Granulocytic protein p25 was found to be a product of oxidative cleavage of disulfide bridges in the p50 dimer. It was shown that neither protein p50 nor the p25 subunit is a degradation product of a protein of higher molecular weight. The N-terminal amino acid sequence of p25 was: RLNYNKPHAA. Binding capacity for double stranded DNA without significant sequence specificity was revealed and nuclear localization of some fraction of p50 dimer was established. The data concerning the cell and species specificity demonstrated that the protein is expressed only in normal human granulocytes. In summary, protein p25 originates from splitting of the p50 dimer. This subunit shows no identity with proteins already sequenced. DNA-binding of p25 is not sequence specific. It is concluded that the protein p50 is localized in the nuclei and cytoplasmic granules of mature human polymorphonuclear leukocytes or granulocytes of species high on the evolutionary tree. The functions of this protein remain to be determined.

Differential expression of nuclear HMG1, HMG2 proteins and H1(zero) histone in various blood cells.

Changes in the levels of chromosomal high-mobility group proteins HMG1, HMG2 and histone H1 zero were investigated in blood cells of various types, proliferation activity and stage of differentiation. The relative amounts of proteins HMG1, HMG2 and histone H1 zero were evaluated densitometrically by SDS-PAGE of 5 per cent w/v perchloric acid extracts of blood cells. Concerning the HMG1 and HMG2, the main conclusions were: the expression of these HMG proteins was higher in malignant cells, namely leukemia cell lines, then in lymphocytes or granulocytes and the distribution of HMG1 and HMG2 was highly cell-specific. In comparison with lymphoid cells, the levels of HMG1/2 were higher in myeloid cells. The results revealed that in myeloid cells HMG2 prevails over HMG1. There was no direct correlation between HMG1/2 expression and proliferation activity. The levels of HMG1/2 did not depend on the transcription of chromatin either. However, there was some connection between irreversibly differentiated nonproliferating cells and a loss of HMG1/2 proteins. Reversibly differentiated leukemic cells retain their HMG1/2 levels. Similarly to HMG1/2,H1 zero showed a strong cell specificity. The level of H1 zero was different in the various blood cell types. As compared with lymphoid cells, the level of H1 zero was several-fold higher in myeloid cells, regardless of whether they were normal or malignant. Moreover, there was an accumulation of H1 zero in differentiating HL-60 cells accompanied by only a slight decline in cell proliferation; this agrees with the idea that H1 zero expression is not directly associated with the inhibition of cell growth. Rather higher expression of H1 zero is related to changes during cell differentiation.

Expression of chromosomal protein HMG-1 in transformed and normal human cells.

Western blot analysis showed differences in the expression of chromosomal high mobility group protein (HMG-1) in human leukemic cell lines and normal peripheral nonproliferating leukocytes. The amount of HMG-1 was increased in fast growing transformed cells. The data suggest that HMG-1 has an important function in cell proliferation.

The interaction of human hemoglobin with erythrosin. Comparison of hemoglobins with variously liganded heme groups.

The interactions of erythrosin with deoxyhemoglobin, oxyhemoglobin, carbonmonoxyhemoglobin, methemoglobin, cyanomethemoglobin and hemoglobin alpha and beta chains have been studied by using the equilibrium dialysis, the difference and circular dichroic (CD) spectra and stopped-flow method. The values of equilibrium and kinetic parameters, as well as CD characteristics, show that in addition to a number of weak binding sites hemoglobin contain four, relatively strong binding sites, one per chain. The properties of the strong binding sites depend on the ligand of the heme group and the charge of the heme group is not directly responsible for this fact. Consequently the properties of deoxyhemoglobin and methemoglobin, differing from the mutually close properties of the other derivatives, confirm that the state of the heme group affects the conformation of hemoglobin molecules in solution. These results are in a good agreement with the classification established on the heme iron spin state.

The binding of chloramphenicol to serum proteins in patients with chronic renal insufficiency.

The binding (r) of chloramphenicol to serum proteins is significantly lower in patients with chronic renal failure than in normal subjects. Before hemodialysis, the mean r value in patients with chronic renal insufficiency was 0.165 mg/g (+/-0.003) versus 0.188 mg/g (+/-0.004) in healthy individuals. Hemodialysis produced a significant rise in r (to 0.182 mg/g, +/-0.004). Decrease in the serum concentration of albumin in patients with chronic renal insufficiency does not seem to be the sole factor responsible for decreased r.