Jacek Przybylski

Tonic activity of carotid body chemoreceptors contributes to the increased sympathetic drive in essential hypertension

Carotid chemoreceptors provoke an increase in muscle sympathetic nerve activation (MSNA) in response to hypoxia; they are also tonically active during normoxic breathing. The contribution of peripheral chemoreceptors to sympathetic activation in hypertension is incompletely understood. The aim of our study was to investigate the effect of chemoreceptor deactivation on sympathetic activity in untreated patients with hypertension. A total of 12 untreated hypertensive males and 11 male controls participated in this randomized, crossover, placebo-controlled study. MSNA, systolic blood pressure(BP), diastolic BP, heart rate (HR), electrocardiogram, hemoglobin oxygen saturation (Sat%) and respiratory movements were measured during repeated 10-min periods of respiration with 100% oxygen or 21% oxygen in a blinded fashion. Compared with controls, hypertensives had higher resting MSNA (38±10 vs. 29±0.9 burst per min, P<0.05), systolic BP (150±12 vs. 124±10 mm Hg, P< 0.001) and diastolic BP (92±10 vs. 77±9 mm Hg, P<0.005). Breathing 100% oxygen caused significant decrease in MSNA in hypertensive patients (38±10 vs. 26±8 burst per min and 100±0 vs. 90±10 arbitrary units, P<0.05) and no change in controls (29±9 vs. 27±7 burst per min and 100±0 vs. 96±11 arbitrary units). BP, respiratory frequency and end tidal CO2 did not change during chemoreceptor deactivation with hyperoxia. HR decreased and Sat% increased in both the study groups. These results confirm the role of tonic chemoreceptor drive in the development of sympathetic overactivity in hypertension.

Sexual behavior in male rats after nitric oxide synthesis inhibition

The influence of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the copulatory behavior of sexually experienced male Wistar rats was investigated. L-NAME was injected i.p. 10 min before the onset of a session using a dose of 30 mg/kg (L-NAME 30 group), or 60 mg/kg (L-NAME 60 group). The copulatory sessions were terminated after the third ejaculation in the control group or after 1500 s in the L-NAME 30 and L-NAME 60 groups. L-NAME administration reduced the number of rats that achieved ejaculation by 43% and 86% in the L-NAME 30 and 60 groups, respectively. In both experimental groups only a few intromissions and an increased number of mountings were observed. An increase in the number of ultrasonic vocalizations in the 50 kHz band, a dose-dependent effect, was observed. The level of sexual motivation evaluated by mount latency was not influenced by inhibition of NO synthesis.

Effect of substrate stiffness on the osteogenic differentiation of bone marrow stem cells and bone-derived cells.

There is a profound dependence of cell behaviour on the stiffness of its microenvironment. To gain a better understanding of the regulation of cellular differentiation by mechanical cues, we investigated the influence of matrix stiffness (E = 1.46 kPa and E = 26.12 kPa) on differentiated osteogenic cell lineage of bone marrow stem cells (BM‐MSCs) and bone‐derived cells (BDCs) using flexible collagen‐coated polyacrylamide substrates. Differentiation potential was determined by measuring alkaline phosphatase activity, expression of osteoblast‐specific markers including alkaline phosphatase, osteocalcin, Runx2 and collagen type I, as well as assessment of mineralisation (Alizarin Red S staining). We found that osteogenic differentiation can be regulated by the rigidity of the substrate, which may depend on the commitment in multi‐ or uni‐potent targeting cells. Osteogenic differentiation of BM‐MSCs was enhanced on a stiff substrate compared to a soft one, whereas BDCs osteogenic differentiation did not vary depending on the substrate stiffness. The data help in understanding the role of the external mechanical determinants in stem cell differentiation, and can also be useful in translational approach in functional tissue engineering.

Candidate bone-tissue-engineered product based on human-bone-derived cells and polyurethane scaffold.

Biodegradable polyurethanes (PURs) have recently been investigated as candidate materials for bone regenerative medicine. There are promising reports documenting the biocompatibility of selected PURs in vivo and the tolerance of certain cells toward PURs in vitro - potentially to be used as scaffolds for tissue-engineered products (TEPs). The aim of the present study was to take a step forward and create a TEP using human osteogenic cells and a polyurethane scaffold, and to evaluate the quality of the obtained TEP in vivo. Human-bone-derived cells (HBDCs) were seeded and cultured on polyurethane scaffolds in a bioreactor for 14 days. The TEP examination in vitro was based on the evaluation of cell number, cell phenotype and cell distribution within the scaffold. TEPs and control samples (scaffolds without cells) were implanted subcutaneously into SCID mice for 4 and 13 weeks. Explants harvested from the animals were examined using histological and immunohistochemical methods. They were also tested in mechanical trials. It was found that dynamic conditions for cell seeding and culture enable homogeneous distribution, maintaining the proliferative potential and osteogenic phenotype of the HBDCs cultured on polyurethane scaffolds. It was also found that HBDCs implanted as a component of TEP survived and kept their ability to produce the specific human bone extracellular matrix, which resulted in higher mechanical properties of the harvested explants when preseeded with HBDCs. The whole system, including the investigated PUR scaffold and the method of human cell seeding and culture, is recommended as a candidate bone TEP.

Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients

Previous studies have shown that hyperoxia-induced deactivation of carotid body chemoreceptors reduces sympathetic activity in hypertensive patients but it does not affect blood pressure. The maintenance of blood pressure can be explained by the direct, vasoconstrictive effect of hyperoxia, which offsets diminished sympathetic activity. This study compares the effect of acute hyperoxia on hemodynamic parameters between hypertensive and normotensive subjects. Twelve males with hypertension (age 39.4±2.4 years; body mass index 27.4±1.1 kg m−2) and 11 normotensive males (age 39.9±2.7 years; body mass index 25.4±0.7 kg m−2) received, via non-rebreathing mask ventilation, ambient air, followed by 100% oxygen for 20 min. The stroke volume, heart rate, cardiac output, blood pressure, total peripheral resistance, respiratory rate, baroreceptor control of heart rate and oxygen saturation were recorded continuously. Several 30 s periods were analyzed before, during and after inducing hyperoxia. At baseline, the hypertensive subject’s blood pressure was higher and their baroreflex control of heart rate was lower when compared with the normotensive control group. After the first 30 s of hyperoxia, systolic, diastolic and mean blood pressures, as well as the total peripheral resistance, decreased significantly in hypertensives but not in normotensives. After 20 min of 100% oxygen ventilation, systolic and mean blood pressures and total peripheral resistance was increased in hypertensive patients, and the cardiac output and stroke volume had decreased in both groups. The results of this study confirm that deactivation of carotid body chemoreceptors can acutely decrease blood pressure in humans.

KIDNEY DENERVATION COMBINED WITH ELIMINATION OF ADRENAL–RENAL PORTAL CIRCULATION PREVENTS THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

1. Kidney denervation in spontaneously hypertensive rats (SHR) during the prehypertensive stage delays and attenuates the development of hypertension. The same results have been obtained after elimination of the adrenal–renal portal circulation (ARPC). The aim of the present study was to investigate the influence of concomitant kidney denervation and elimination of ARPC on hypertension in SHR.

Heart Rate and Respiratory Rate Influence on Heart Rate Variability Repeatability: Effects of the Correction for the Prevailing Heart Rate

Background: Since heart rate variability (HRV) is associated with average heart rate (HR) and respiratory rate (RespRate), alterations in these parameters may impose changes in HRV. Hence the repeatability of HRV measurements may be affected by differences in HR and RespRate. The study aimed to evaluate HRV repeatability and its association with changes in HR and RespRate. Methods: Forty healthy volunteers underwent two ECG examinations 7 days apart. Standard HRV indices were calculated from 5-min ECG recordings. The ECG-derived respiration signal was estimated to assess RespRate. To investigate HR impact on HRV, HRV parameters were corrected for prevailing HR. Results: Differences in HRV parameters between the measurements were associated with the changes in HR and RespRate. However, in multiple regression analysis only HR alteration proved to be independent determinant of the HRV differences—every change in HR by 1 bpm changed HRV values by 16.5% on average. After overall removal of HR impact on HRV, coefficients of variation of the HRV parameters significantly dropped on average by 26.8% (p < 0.001), i.e., by the same extent HRV reproducibility improved. Additionally, the HRV correction for HR decreased association between RespRate and HRV. Conclusions: In stable conditions, HR but not RespRate is the most powerful factor determining HRV reproducibility and even a minimal change of HR may considerably alter HRV. However, the removal of HR impact may significantly improve HRV repeatability. The association between HRV and RespRate seems to be, at least in part, HR dependent.

Occlusion of the adrenal vein leads to an increase in renal vascular resistance in the ipsilateral kidney.

1. The aim of the present study was to investigate the effect of an acute increase in blood flow through the adrenal‐renal vascular connection (ARVC), due to occlusion of the adrenal vein, on renal blood flow (RBF) and renal vascular resistance (RVR).

Selected tumor markers in the routine diagnosis of chromophobe renal cell carcinoma

Renal cell carcinoma is one of the most malignant tumors, affecting men more frequently than women and constituting nearly 90% of all kidney tumors. Chromophobe renal cell carcinoma has been described as a new histological type of renal cell carcinoma. Chromophobe renal cell carcinoma constitutes up to 5% of all cases of kidney cancer. It is characterized by a significant number of deletions in many chromosomes, as well as the loss of entire chromosomes. Chromophobe renal cell carcinoma arises from tubular cells or cells of the macula densa. In contrast to other types of kidney cancer, it occurs with equal frequency in men and women, mostly in the sixth decade of life. It is characterized by a relatively good prognosis and exhibits a low degree of malignancy. Histopathologic diagnosis of ChRCC can be a diagnostic challenge because these tumors may resemble oncocytoma or conventional cancer. Research by Mathers et al. proposed the use of cytokeratin 7 as a marker useful in the differentiation of these changes.

The Most Important Transcriptional Factors of Osteoblastogenesis

Summary One of the key issues of organogenesis is the understanding of mechanisms underlying the differentiation of progenitor cells into more specialized cells of individual tissues. Recent transcriptomic and proteomic approaches of molecular biology have led to the identification of several factors and mechanisms regulating morphogenesis at the genetic level which affect the function of already differentiated cells. In the last few years, several reports about osteoblastogenesis have been published. This review presents recent findings on the role of the most important transcription factors supporting bone formation.