Intensive chemotherapy perturbs heart rate variability in children with cancer.

OBJECTIVES: In children, cancer chemotherapy may impair the functioning of the cardiac autonomic nervous system. Moreover, it is not known whether there are any differences between intensive and maintenance phases of chemotherapy. Therefore, the aim of the current study was to assess autonomic nervous system activity using heart rate variability, in children receiving intensive or maintenance cancer chemotherapy. METHODS: For that purpose, children who were healthy (healthy control, n = 30), receiving intensive chemotherapy (chemotherapy, n = 30), and receiving maintenance chemotherapy (maintenance, n = 25) were included in the study. Autonomic nervous system activity was measured by means of heart rate variability. Electrocardiogram recordings were used to calculate time- and frequency-domain heart rate variability parameters. RESULTS: Time-domain parameters such as standard deviation of NN intervals and frequency-domain parameters such as total power were lower during the intensive chemotherapy but not during maintenance phase (standard deviation of NN intervals: 50±5, 33±3, and 48±3 ms, and total power: 2613±504, 1379±296 and 2295±264 ms2, respectively for healthy control, chemotherapy and maintenance groups, P<0.001 for both standard deviation of NN intervals and total power). DISCUSSION: The present results indicate that intensive chemotherapy perturbs the function of heart rate variability in children, with recovery during the maintenance phase. This suggests that intensive chemotherapy is likely to affect the autonomic nervous system but this effect does not appear to be permanent.

Autonomic nervous system activity under rotational shift programs: effects of shift period and gender.

Rotational shifts perturb homeostatic mechanisms in a sexually dimorphic way and may compromise the activity of the autonomic nervous system during day- and night-shifts. Heart rate variability (HRV) is a non-invasive measure to assess autonomic control of the heart. Our aim in this study was to assess HRV by short-term continuous electrocardiogram in female (n=40, average age: 31, average working year: 7) and male (n=40, average age: 29, average working year: 6) nurses under rotational shift programs, HRV is derived from short-term electrocardiogram recordings, carried out both at day- and night -shifts, and included time-domain [e.g., standard deviation of NN intervals, SDNN (ms); percentage of successive RR intervals that differ by more than 50 ms, pNN50 (%); root mean square of successive RR interval differences, RMSSD (ms)] and frequency-domain [very low frequency, VLF; low frequency, LF; high frequency, HF; LF/HF] parameters. Heart rates were similar across the groups but males had lower SDNN (p=0.020), RMSSD (p=0.001). pNN50 (p=0.001), VLF (p=0.048) and HF (p=0.001) but had higher LF/HF ratio (p=0.000) than females. In general, these parameters did not differ between day- and night-shifts (p<0.05). Lower HRV parameters and higher LF/HF in males suggest that they may be under greater threat for disease progression.

Erythrocyte transfusion restored heart rate variability in children with thalassemia major.

Thalassemia major (TM) is a severe transfusion-dependent anemia. Regular erytrocyte transfusion is required for the treatment of thalassemia patients. However, repeated transfusion may result in impairements in heart function. In this study, we aimed to investigate short-term effects of erythrocyte transfusion on autonomic control of heart in children with thalassemia major. For that purpose heart rate variability (HRV), which is a non-invasive method used to evaluate the effects of the autonomic nervous system on the heart rhythym, was measured before and after erythrocyte transfusion and compared to the healthy controls. Children diagnosed with TM (n = 17) and sex and age matched healthy children (HC, n = 30) were included in the study. HRV values of TM patients were measured 5 min before erythrocyte transfusion (BET, n = 17) and 5 min after erythrocyte transfusion (AET, n = 17). Parameters of time-domain and frequency-domain of HRV were evaluated in all participants. Heart rate (HR) was higher in the BET than AET (P = 0.002) but there was no difference between AET and HC groups (P > 0.05). HRV parameters were lower in BET than AET (P < 0.05) but there were no statistical difference between AET and HC (P> 0.05). The data suggest that, in thalassemia major patients, erythrocyte transfusion restores HR and HRV parameters to the levels observed in healthy controls and, thus, in short-terms, appears to be beneficial for the autonomic control of the heart.

Effects of Half- or Whole-Night Shifts on Physiological and Cognitive Parameters in Women.

BACKGROUND: The study assessed the effects of whole- or half-night shifts on leptin, melatonin, sex hormones, interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, hematological parameters, sleep quality and attentional performance in women working in the health sector. MATERIALS AND METHODS: Women working whole-night shifts (16:00-08:00 hours, n = 20), half-night shifts (16:00-24:00 hours, n = 20) or day shifts (08:00-16:00 hours, n = 20) participated in the study. Blood pressure, respiratory rate, proximal skin temperature (forehead), blood glucose, leptin, melatonin, estradiol, progesterone, IL-1ß, TNF-α, and IL-6 concentrations, complete blood count and erythrocyte sedimentation rate (ESR) were measured in the beginning and at the end of the shifts. The participants filled in sleep quality questionnaires and performed visual attention tests. RESULTS: Half- and whole-night shifts caused problems in sleep duration and quality and disturbed the melatonin rhythm. Women working both half- and whole-night shifts had significantly higher nucleated erythrocytes (P = 0.006), eosinophils (P = 0.031), lymphocytes (P = 0.001) and leptin concentrations (P = 0.001) but had lower ESR (P = 0.046) and neutrophil percentage (P = 0.001) than that of day-time workers. Whole-night shifts caused additional changes including lower attentional performance (P = 0.035), lower platelet counts (P = 0.000) and lower estradiol levels (P = 0.029), but higher TNF-α levels (P = 0.000), than the control group. Moreover, whole-night shifts increased IL-1ß levels before the shift (P < 0.001) and increased IL-6 levels over the half-night shifts (P < 0.05). CONCLUSIONS: Half-night shifts disturbed sleep parameters and the melatonin rhythm, perturbed blood cell turnover and increased leptin levels. Whole-night shifts caused additional problems including suppressed estradiol, activated inflammatory responses and decreased visual attention. All together, the data suggest that night shifts, especially whole-night shifts, should be refrained from or countermeasures should be taken.

The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats.

Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response. In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. In the present study, Sprague-Dawley rats were divided into 5 groups (i.e. the Sham, CLP, JWH-133 0.2 mg/kg, JWH-133 1 mg/kg, and JWH-133 5 mg/kg Groups). Except for the Sham Group, the CLP-induced sepsis model was applied to all groups. The histopathological damage in brain, lung, liver and, heart was examined and the caspase-3, p-NF-κB, TNF-α, IL-1ß and IL-6 levels were determined immunohistochemically. The serum TNF-α, IL-1ß, IL-6, IL-10 levels were examined with the ELISA Method. The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1ß, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1ß, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels. In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart. Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.

The protective effect of cannabinoid type 2 receptor activation on renal ischemia-reperfusion injury.

Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n = 45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-κB, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.

Effects of noopept on cognitive functions and pubertal process in rats with diabetes.

AIM: Type 1 diabetes (T1DM) is a common chronic disease in childhood. Increasing insulin resistance in puberty gives rise to higher doses of insulin usage in treatment. Of this reason new approaches in treatment are needed. Noopept researches suggest it to have anti-diabetic properties. We tried to determine the effects of noopept on pubertal diabetes. MAIN METHOD: The research was made with 60 prepubertal, 28 day-old, male, Sprague Dawley rats. The rats were divided into randomised 6 groups (n = 10/group). i) Control, ii) Diabetes Control, iii) Noopept Control, iv) Diabetes + Noopept, v) Diabetes + Insulin, vi) Diabetes + Insulin + Noopept. T1DM model was induced by streptozotocin on postnatal 28th day. 0.5 mg/kg noopept and 1 IU insulin were administered intraperitoneally for 14 days. Blood glucose and body weight measurements, puberty follow-up and MWM tests were performed. Hippocampus, hypothalamus and testis were evaluated histologically. Hypothalamic GnRH and kisspeptin were studied immunohistochemically. Serum LH, FSH and insulin, hippocampal homogenate NGF and BDNF levels were determined by ELISA. KEY FINDINGS: Delayed puberty was normalized by noopept (p < 0.05). Blood glucose levels were lower in noopept-administered diabetic groups (p < 0.05). Noopept decreased HOMA-IR in insulin administered diabetic group (p < 0.05). Number of degenerated cells in hippocampus and testis were higher in diabetes control group when compared with other groups (p < 0.05). GnRH immunoreactivity in Diabetes + Noopept group was increased when compared to insulin + noopept group (p = 0.018). There was no difference in kisspeptin, serum LH, FSH, hippocampal NGF-BDNF levels and spatial learning assessment among groups (p > 0.05). SIGNIFICANCE: Noopept may have positive effect in treatment of pubertal diabetes.

Long-term metabolic cage housing increases anxiety/depression-related behaviours in adult male rats.

There are several reports on unfavourable effects of metabolic cage housing on animal welfare mainly due to the characteristic structures of these cages such as single housing and grid flooring. This study was aimed to compare the effects of long-term metabolic cage housing and conventional housing (normal grouped housing in standard cages) on the anxiety/depression-like behaviours in male rats. Anxiety/depression-related behaviours were evaluated by use of forced swimming test and open field test. Swimming and climbing were significantly lower and immobility duration higher in the metabolic cage group. In the open field test, total distance, mean velocity, time spent in the central area, zone transition, grooming, and rearing scores were significantly lower in the metabolic cage. Moreover, serum corticosterone level was higher in the metabolic cage group. The results of the study indicate that long-term metabolic cage housing may cause an increase in the anxiety- and depression-related behaviours in male rats.

Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury.

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-( p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.

Maternal viral mimetic administration at the beginning of fetal hypothalamic nuclei development accelerates puberty in female rat offspring.

This study aimed to investigate the effects of maternal viral infection during a critical time window of fetal hypothalamic development on timing of puberty in the female offspring. For that purpose, a viral mimetic (i.e., synthetic double-strand RNA, namely, polyinosinic-polycytidylic acid, poly (I:C)) or saline was injected (i.p.) to the pregnant rats during the beginning (day 12 of pregnancy, n = 5 for each group) or at the end of this time window (day 14 of pregnancy, n = 5 for each group). Four study groups were formed from the female pups (n = 9-10 pups/group). Following weaning of pups, vaginal opening and vaginal smearing was studied daily until 2 sequential estrous cycles were observed. During the second diestrus phase, blood samples were taken for progesterone, leptin, corticosterone, follicle-stimulating hormone, and luteinizing hormone. Maternal poly (I:C) injection on day 12 of pregnancy increased body mass and reduced the time to puberty in the female offspring. Neither poly (I:C) nor timing of injection affected other parameters studied (p > 0.05). It has been shown for the first time that maternal viral infection during the beginning of fetal hypothalamic development might hasten puberty by increasing body mass in rat offspring.