In the past, water homeostasis of the brain was understood as a certain quantitative equilibrium of water content between intravascular, interstitial, and intracellular spaces governed mostly by hydrostatic effects i.e., strictly by physical laws. The recent achievements in molecular bioscience have led to substantial changes in this regard. Some new concepts elaborate the idea that all compartments involved in cerebral fluid homeostasis create a functional continuum with an active and precise regulation of fluid exchange between them rather than only serving as separate fluid receptacles with mere passive diffusion mechanisms, based on hydrostatic pressure. According to these concepts, aquaporin-4 (AQP4) plays the central role in cerebral fluid homeostasis, acting as a water channel protein. The AQP4 not only enables water permeability through the blood-brain barrier but also regulates water exchange between perivascular spaces and the rest of the glymphatic system, described as pan-cerebral fluid pathway interlacing macroscopic cerebrospinal fluid (CSF) spaces with the interstitial fluid of brain tissue. With regards to this, AQP4 makes water shift strongly dependent on active processes including changes in cerebral microcirculation and autoregulation of brain vessels capacity. In this paper, the role of the AQP4 as the gatekeeper, regulating the water exchange between intracellular space, glymphatic system (including the so-called neurovascular units), and intravascular compartment is reviewed. In addition, the new concepts of brain edema as a misbalance in water homeostasis are critically appraised based on the newly described role of AQP4 for fluid permeation. Finally, the relevance of these hypotheses for clinical conditions (including brain trauma and stroke) and for both new and old therapy concepts are analyzed.
Background: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. Materials and methods: Investigated population consisted of 71 patients aged 43–76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for –108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. Results: Significant correlations between diabetes mellitus and paraoxonase activity (R = –0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = –0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. Conclusions: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.
BackgroundAn earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients’ lowered QoL was coupled to a reduction in hippocampal volume.MethodsPatients (11 men and 4 women, age 31–65) treated for head and neck cancer 4–10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 – 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon’s signed rank test were used for the main statistical analysis.ResultsThere was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients.ConclusionThe study gives solid evidence against the hypothesis that the patients’ lowered quality of life was due to a major reduction of hippocampal volume.
Background In patients with end stage renal disease (ESRD), left ventricular (LV) hypertrophy with impaired LV function, which is called uremic cardiomyopathy (UC) is often observed. The UC historically has been considered a contraindication for kidney transplantation (KTx). Currently, moderate LV dysfunction does not exclude the possibility of KTx. The amelioration of uremia after KTx improved cardiac function in patients with LV dysfunction. There is a little information on the function of the left atrium (LA) after the KTx procedure. There are no studies evaluating (LA) changes in patients with UC after KTx and determining the possibility of inhibiting the occurrence of LA unfavourable changes (remodelling) and even a possible LA recovery process (reverse remodelling) as a result of a successful KTx. The aim of the study was to assess the LA reverse remodelling in patients with ESRD undergoing KTx. Methods The study group consisted of 42 patients, aged 43.3 ± 12.6 followed for 36 months after a deceased donor KTx. The patients were studied at five time points: 1, 3, 6, 12 and 36 months after KTx. In all patients transthoracic echocardiography was performed in order to assess the following LA planimetric parameters: LA max , LA min , LA waveP . LA shortmax , LA shortmin , LA shortwaveP , LA longmax , LA longmin , LA longwaveP , LA circmax and LA areamax , volumentric parameters: LA volume (LAV), LA volume index (LAVI), and hemodynamic indices: LA ejection fraction (LA EF ), LA active emptying fraction (LA AE ), LA passive emptying fraction (LA PE ), LA index of expansion (LA IE ) and LA fractional shortening (LA FS ). Results The LAVI values were 34.63 ± 10.34 ml/m 2 , 32.24 ± 9.59 ml/m 2 ( p < 0,001), 31.36 ± 9.20 ml/m 2 ( p < 0,001), 28.29 ± 8.32 ml/m 2 ( p < 0,001) and 27.57 ± 8.40 ml/m 2 ( p < 0,001), after: 1, 3, 6, 12 and 36 months after KTx, respectively. The reduction of the LA size was accompanied by gradual LA contractility improvement, which was manifested as an increase of the LA hemodynamic indices such as LA EF , LA AE , LA IE , LA FS and a decrease of LA PE . Conclusions LA remodelling secondary to ...
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