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1.
Brain Res Bull ; 212: 110955, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38677558

ABSTRACT

In clinical trials for Alzheimer's disease (AD), hydromethylthionine mesylate (HMTM) showed reduced efficacy when administered as an add-on to symptomatic treatments, while it produced a significant improvement of cognitive function when taken as monotherapy. Interference of cholinesterase inhibition with HMTM was observed also in a tau transgenic mouse model, where rivastigmine reduced the pharmacological activity of HMTM at multiple brain levels including hippocampal acetylcholine release, synaptosomal glutamate release and mitochondrial activity. Here, we examined the effect of HMTM, given alone or in combination with the acetylcholinesterase inhibitor, rivastigmine, at the level of expression of selected pre-synaptic proteins (syntaxin-1; SNAP-25, VAMP-2, synaptophysin-1, synapsin-1, α-synuclein) in brain tissue harvested from tau-transgenic Line 1 (L1) and wild-type mice using immunohistochemistry. L1 mice overexpress the tau-core unit that induces tau aggregation and results in an AD-like phenotype. Synaptic proteins were lower in hippocampus and cortex but greater in basal forebrain regions in L1 compared to wild-type mice. HMTM partially normalised the expression pattern of several of these proteins in basal forebrain. This effect was diminished when HMTM was administered in combination with rivastigmine, where mean protein expression seemed supressed. This was further confirmed by group-based correlation network analyses where important levels of co-expression correlations in basal forebrain regions were lost in L1 mice and partially re-established when HMTM was given alone but not in combination with rivastigmine. These data indicate a reduction in pharmacological activity of HMTM when given as an add-on therapy, a result that is consistent with the responses observed in the clinic. Attenuation of the therapeutic effects of HMTM by cholinergic treatments may have important implications for other potential AD therapies.


Subject(s)
Cholinesterase Inhibitors , Disease Models, Animal , Mice, Transgenic , Rivastigmine , Tauopathies , Animals , Tauopathies/drug therapy , Tauopathies/metabolism , Cholinesterase Inhibitors/pharmacology , Rivastigmine/pharmacology , Mice , tau Proteins/metabolism , Synapses/drug effects , Synapses/metabolism , Brain/metabolism , Brain/drug effects , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Male , Methylene Blue/analogs & derivatives
2.
NeuroRehabilitation ; 52(2): 289-298, 2023.
Article in English | MEDLINE | ID: mdl-36641689

ABSTRACT

BACKGROUND: Reduced muscle strength is one symptom of Parkinson's disease (PD). Strength can be increased by strength training, which may cause exaggerated blood pressure (BP) rise. It is believed that exercises performed on vibrating platform can strengthen leg muscles without excessive BP increase. OBJECTIVE: To measure the pressor response to static exercises performed during whole body vibration in PD patients. METHODS: Twenty-four aged PD patients and twelve healthy young volunteers participated in the study. PD subjects performed six repetitions of deep-, semi-squat, and calves at vibration frequency of 30 Hz. Each 30 s exercise was followed by 30 s rest. The young volunteers performed two sessions of above-mentioned exercises with and without vibration. BP was measured continuously. RESULTS: In PD patients, the highest BP values were observed during deep squat; systolic blood pressure rose 10 mmHg in 'weak responders', and 50 mmHg in 'strong responders'. This difference correlated with the rise in pulse pressure suggesting indirectly the role of stoke volume in individual response. In healthy subjects pressor response was also individually differentiated and not influenced by vibration. CONCLUSION: Deep and semi squat can evoke a strong cardiovascular response in some PD and healthy subjects. Low-magnitude vibrations likely did not affect pressor response.


Subject(s)
Parkinson Disease , Vibration , Humans , Animals , Cattle , Aged , Muscle Strength/physiology , Healthy Volunteers , Muscle, Skeletal/physiology
3.
Front Aging Neurosci ; 13: 654931, 2021.
Article in English | MEDLINE | ID: mdl-34326765

ABSTRACT

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

4.
Med Devices (Auckl) ; 14: 165-172, 2021.
Article in English | MEDLINE | ID: mdl-34104008

ABSTRACT

Assessment of autonomic nervous system (ANS) functioning may be performed non-invasively using autonomic tests which are based on evaluation of response of cardiovascular system to the applied stimuli, such as increased air pressure during Valsalva maneuver, skeletal muscle contraction during static handgrip or deep slow breathing. The cardiovascular response depends, besides ANS reaction and test protocol, also on the way stimulus is self-applied by the test subject. We present a versatile device for controlling stimulus self-application during three ANS tests: Valsalva maneuver, static handgrip, and deep breathing. It integrates two different gauges and a pace setter for breathing into one device. The core of the device is a linear LED display which, using green, yellow, and red diodes, informs the subject about the correctness of self-application of respective stimulus. The settings of the device can be adjusted to the needs of the protocol chosen. The device can record the duration of mouth air pressure or the force produced by the subject during ANS tests, which assures correctness of the tests, thus allowing to track individual variability changes in the response to the test. The device was verified during ANS tests and its use was intuitive for patients, reducing the time needed for training before tests and decreasing the effort of the physician.

5.
Life (Basel) ; 11(1)2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33418848

ABSTRACT

Although the mechanisms of toxic activity of tau are not fully recognized, it is supposed that the tau toxicity is related rather not to insoluble tau aggregates but to its intermediate forms. It seems that neurofibrillar tangles (NFTs) themselves, despite being composed of toxic tau, are probably neither necessary nor sufficient for tau-induced neuronal dysfunction and toxicity. Tau oligomers (TauOs) formed during the early stages of tau aggregation are the pathological forms that play a key role in eliciting the loss of neurons and behavioral impairments in several neurodegenerative disorders called tauopathies. They can be found in tauopathic diseases, the most common of which is Alzheimer's disease (AD). Evidence of co-occurrence of b-amyloid, α-synuclein, and tau into their most toxic forms, i.e., oligomers, suggests that these species interact and influence each other's aggregation in several tauopathies. The mechanism responsible for oligomeric tau neurotoxicity is a subject of intensive investigation. In this review, we summarize the most recent literature on the damaging effect of TauOs on the stability of the genome and the function of the nucleus, energy production and mitochondrial function, cell signaling and synaptic plasticity, the microtubule assembly, neuronal cytoskeleton and axonal transport, and the effectiveness of the protein degradation system.

6.
Ginekol Pol ; 91(4): 216-222, 2020.
Article in English | MEDLINE | ID: mdl-32374022

ABSTRACT

OBJECTIVES: The aim of the study was to assess the utility of mid-trimester ultrasound parameters in predicting birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. RESULTS: There is a correlation between the birth weight and ultrasound-ascertained parameters, including those characterising uterine artery blood flow and foetal biometry [abdominal circumference (AC), femoral length (FL), biparietal dimension (BPD)].The biparietal dimension (BPD), head circumference (HC) abdominal circumference (AC) and pre-existing diabetes are the ultrasound predictors of LGA. The presence of an early-diastolic uterine artery blood flow waveform notching, as well as the uterine artery pulsatility index (UAPI), femoral length (FL) and hypertension in pregnancy are the ultrasound predictors of SGA. In the subset of women with pre-gestational diabetes (PGDM), there is a negative correlation between the birth weight and the uterine artery pulsatility index and early-diastolic uterine artery blood flow waveform notching. In women with pre-gestational diabetes mellitus (PGDM), femoral length (FL) is a significant predictor of LGA and in case of SGA significant predictors are uterine artery pulsatility index, artery blood flow waveform notching and femoral length (FL). CONCLUSIONS: Midtrimester ultrasound parameters with confirmed usefulness in the prediction of birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus include: uterine artery PI, early-diastolic uterine artery blood flow waveform notching and foetal biometry.


Subject(s)
Diabetes, Gestational/diagnostic imaging , Pregnancy in Diabetics/diagnostic imaging , Pregnancy, High-Risk , Uterine Artery/diagnostic imaging , Adult , Birth Weight , Case-Control Studies , Female , Humans , Pregnancy , Pregnancy Complications/diagnostic imaging , Pregnancy Trimester, Second , Ultrasonography, Prenatal/methods
7.
Int J Mol Sci ; 21(3)2020 Feb 10.
Article in English | MEDLINE | ID: mdl-32050617

ABSTRACT

Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson's disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient's brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.


Subject(s)
Brain-Derived Neurotrophic Factor/therapeutic use , Neuroprotective Agents/therapeutic use , Parkinson Disease/drug therapy , Animals , Brain-Derived Neurotrophic Factor/metabolism , Humans , Parkinson Disease/metabolism
8.
Front Neurol ; 10: 1143, 2019.
Article in English | MEDLINE | ID: mdl-31736859

ABSTRACT

Parkinson's disease (PD) is manifested by progressive motor, autonomic, and cognitive disturbances. Dopamine (DA) synthesizing neurons in the substantia nigra (SN) degenerate, causing a decline in DA level in the striatum that leads to the characteristic movement disorders. A disease-modifying therapy to arrest PD progression remains unattainable with current pharmacotherapies, most of which cause severe side effects and lose their efficacy with time. For this reason, there is a need to seek new therapies supporting the pharmacological treatment of PD. Motor therapy is recommended for pharmacologically treated PD patients as it alleviates the symptoms. Molecular mechanisms behind the beneficial effects of motor therapy are unknown, nor is it known whether such therapy may be neuroprotective in PD patients. Due to obvious limitations, human studies are unlikely to answer these questions; therefore, the use of animal models of PD seems indispensable. Motor therapy in animal models of PD characterized by the loss of dopaminergic neurons has neuroprotective and neuroregenerative effects, and the completeness of neuronal protection may depend on (i) degree of neuronal loss, (ii) duration and intensity of exercise, and (iii) time elapsed between insult and commencing of training. As the physical activity is neuroprotective for dopaminergic neurons, the question arises what is the mechanism of this protective action. A current hypothesis assumes a central role of neurotrophic factors in the neuroprotection of dopaminergic neurons, even though it is still not clear whether increased DA level in the nigrostriatal axis results from neurogenesis of dopaminergic neurons in the SN, recovery of the phenotype of dopaminergic neurons, increased sprouting of the residual dopaminergic axons in the striatum, or generation of local striatal neurons from inhibitory interneurons. In the present review, we discuss studies describing the influence of physical exercise on the PD-like changes manifested in animal models of the disease and focus our interest on the current state of knowledge on the mechanism of neuroprotection induced by physical activity as a supportive therapy in PD.

9.
Ginekol Pol ; 90(7): 388-395, 2019.
Article in English | MEDLINE | ID: mdl-31392708

ABSTRACT

OBJECTIVES: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels. RESULTS: Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI. CONCLUSIONS: LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.


Subject(s)
Birth Weight/physiology , Diabetes Mellitus, Type 1/physiopathology , Fetal Macrosomia/diagnosis , Placenta/physiopathology , Pregnancy in Diabetics/physiopathology , Adult , Blood Pressure/physiology , Body Mass Index , Diabetes Mellitus, Type 1/diagnostic imaging , Female , Fetal Macrosomia/etiology , Fetal Macrosomia/physiopathology , Humans , Infant, Newborn , Maternal Age , Placenta/diagnostic imaging , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, First , Pregnancy in Diabetics/diagnostic imaging , Prognosis , Risk Factors , Ultrasonography, Prenatal , Young Adult
10.
Auton Neurosci ; 220: 102555, 2019 09.
Article in English | MEDLINE | ID: mdl-31331695

ABSTRACT

PURPOSE: Long-term ß-adrenolytics treatment in takotsubo syndrome (TTS) patients is based on the premise, that TTS is strongly associated with sympathetic nervous system overactivity. The aim of the study was to establish hemodynamic response to tilt, handgrip and Valsalva manoeuvre in patients with takotsubo syndrome compared to healthy subjects (CONTROL) and patients after ST Elevation Myocardial Infarction (STEMI). MATERIAL AND METHOD: Echocardiographic examination was performed at rest, ECG and continuously non-invasively measured arterial blood pressure were used for evaluation of hemodynamic responses to Valsalva manoeuvre, static handgrip (HG) followed by post-exercise ischemia, and tilt. Ten healthy women, 20 with TTS and 20 after STEMI, mean age 64 ±â€¯8.5 years, participated in the study. RESULTS: Pressor response to Valsalva manoeuvre and tilt in TTS group was diminished in comparison to CONTROL and close to that of STEMI. During HG, increase of SBP was the lowest in TTS group. Data indirectly suggest that it was due to deficient stroke volume in TTS and STEMI patients during these manoeuvres; though echocardiographic findings at rest did not reveal any significant differences between groups. CONCLUSIONS: Our data show that despite apparent resolution of the immediate effects of TTS, impaired response to cardiovascular challenge, similar to that in STEMI patients, persisted. As the manoeuvres applied mimic daily life situations, causes of impairment should be searched for and potential health risk evaluated.


Subject(s)
Blood Pressure/physiology , Hand Strength/physiology , Heart Rate/physiology , Sympathetic Nervous System/physiopathology , Takotsubo Cardiomyopathy/physiopathology , Tilt-Table Test , Valsalva Maneuver/physiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Echocardiography , Female , Humans , Middle Aged , ST Elevation Myocardial Infarction/physiopathology
11.
Neural Plast ; 2019: 8215017, 2019.
Article in English | MEDLINE | ID: mdl-31073303

ABSTRACT

Physical training confers protection to dopaminergic neurons in rodent models of parkinsonism produced by neurotoxins. The sparing effect of physical training on dopaminergic neurons can be tested with training applied during chronic MPTP treatment, while the neurorestorative effect when training is applied after completing such treatment. In this study, the effect of the onset of training respective to chronic MPTP treatment was specifically addressed. Three groups of mice were injected with 10 doses of MPTP (12.5 mg/kg/injection) over 5 weeks. The first group remained sedentary; the second one underwent early onset training, which started 1 week before commencing MPTP treatment, continued throughout 5 weeks of treatment and 4 weeks thereafter; the third group underwent late-onset training of the same length and intensity as the former group, except that it started immediately after the end of MPTP treatment. Two groups served as controls: a saline-injected group that remained sedentary and saline-injected group, which underwent the same training as the early and late-onset training groups. Both early and late-onset physical training saved almost all nigral and VTA dopaminergic neurons, prevented inflammatory response, and increased the BDNF and GDNF levels to a similar extent. From these results one may conclude that early and late-onset training schedules were equipotent in their neuroprotective effect and that the mechanism of neuroprotection was similar. The sparing effect of early onset training may be satisfactorily explained by assuming that the increased level of BDNF and GDNF prevented the degeneration of dopaminergic neurons. To explain a similar number of dopaminergic neurons detected at the end of the early and late-onset training, one should additionally assume that the former training schedule induced neurogenesis. Results of this study support the view that physical activity may be neuroprotective even at a more advanced stage of PD and justify starting physical activity at any point of the disease.


Subject(s)
Dopaminergic Neurons/physiology , Exercise Therapy , Neuronal Plasticity , Parkinson Disease/prevention & control , Parkinson Disease/physiopathology , Animals , Astrocytes/physiology , Chronic Disease/prevention & control , Disease Models, Animal , Male , Mice, Inbred C57BL , Microglia/physiology , Parkinsonian Disorders/physiopathology , Parkinsonian Disorders/prevention & control , Pars Compacta/physiopathology , Ventral Tegmental Area/physiopathology
12.
J Neurosci Methods ; 319: 47-59, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30448465

ABSTRACT

Background Tauopathies, including Alzheimer's disease (AD), are multifactorial diseases with strong phenotypic and genetic heterogeneity. Recent evidence revealed that mechanisms of pathogenesis of early (hereditary) and late (sporadic) forms of AD are different. This is not properly reflected in current experimental models, especially when it comes to sporadic forms of AD. Here, we present novel seeding based model and explore its suitability for therapeutic intervention. New method We validate novel region specific approach to modelling Tau pathology reported by Koss and co-authors (2015). Wistar rats 3, 9 and 15 month-old were surgically prepared for hippocampal loading with pore-former polymeric 1,3-alkylpyridinium salts (Poly-APS) and recombinant human tau including pharmacological inhibition of phosphatase activity by okadaic acid co-administration. We explored whether tau seeding caused molecular and behavioural traits reminiscent of AD and explored their reversibility/prevention by administration of either memantine or lithium. Results The presented model emulates several changes observed in progressive dementia such as: heightened levels of tau and its hyperphosphorylation, changes in tau compartmentalization, breakdown of the cytoskeleton, cognitive impairments, and sensitivity for anti-dementia treatment. Comparison with existing methods Seeding has been achieved in transgenic mouse models, but this is the first rat model significantly mimicking cognitive and neuronal changes akin to tauopathies. Moreover, we have successfully included the factor age in our model and can show sensitivity to drug treatment. Conclusions These data validate a novel model of locally infused recombinant human Tau as an inducer of tauopathy in rats and holds the potential for development of novel therapies.


Subject(s)
CA1 Region, Hippocampal/metabolism , Disease Models, Animal , Lithium Chloride/administration & dosage , Memantine/administration & dosage , Neuroprotective Agents/administration & dosage , Polymers/metabolism , Pyridinium Compounds/metabolism , Tauopathies/metabolism , tau Proteins/metabolism , Alzheimer Disease/metabolism , Animals , CA1 Region, Hippocampal/drug effects , Male , Neurons/drug effects , Neurons/metabolism , Phosphorylation , Polymers/administration & dosage , Pyridinium Compounds/administration & dosage , Rats, Wistar , Recombinant Proteins/metabolism
13.
Postepy Hig Med Dosw (Online) ; 71(1): 713-726, 2017 Jan 04.
Article in English | MEDLINE | ID: mdl-28894046

ABSTRACT

Glial cells and neurotrophins play an important role in maintaining homeostasis of the CNS. Disturbances of their function can lead to a number of nervous system diseases, including Parkinson's disease (PD). Current clinical studies provide evidence that moderate physical activity adapted to the health status of PD patients can support pharmacological treatment, slow down the onset of motor impairments, and extend the patients period of independence. Physical activity, by stimulating the production and release of endogenous trophic factors, prevents the neurodegeneration of dopaminergic neurons via inhibition of inflammatory processes and the reduction of oxidative stress. The aim of this study is to present the current state of knowledge for the anti-inflammatory and neuroprotective properties of physical activity as a supportive therapy in Parkinson's disease.


Subject(s)
Exercise , Inflammation , Neuroprotection , Parkinson Disease/therapy , Anti-Inflammatory Agents/therapeutic use , Humans , Nerve Growth Factors , Neuroglia , Oxidative Stress
14.
Free Radic Biol Med ; 108: 517-523, 2017 07.
Article in English | MEDLINE | ID: mdl-28428000

ABSTRACT

The primary objective in modern obstetrics and prenatal diagnosis is to predict risks of congenital abnormalities. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the risk of foetal chromosomal aberration evaluated at the first trimester screening. A series of studies show that balanced free radical activity and oxidative homeostasis are essential for proper bodily growth and function. Reactive oxygen species (ROS) may be one of the factors associated with disruption of cell cycle and tissue development, thus leading to developmental abnormalities. That's why it's so important to examine connection between level of oxidative stress and congenital abnormalities. Using ultrasonography examinations between 11-13+6d gestational weeks combined with serum levels of pregnancy associated plasma protein A and human chorionic gonadotropin and spectrophotometric analysis of oxidative stress markers such as glutathione (GSH), S-transferase, S-nitrosothiols (RSNO), trolox equivalent antioxidant capacity (TEAC), protein and nitrites we tried to find correlation between birth defects and oxidative stress status. In conclusion, our analysis suggests that elevated maternal serum levels of protein, S-transferase and TEAC as well as decreased maternal serum levels of GSH and protein correlated with the risk of chromosomal aberrations and congenital developmental defects in a foetus.


Subject(s)
Biomarkers/blood , Congenital Abnormalities/diagnosis , Glutathione Transferase/blood , Glutathione/blood , Adult , Chorionic Gonadotropin/blood , Chromosome Aberrations , Congenital Abnormalities/epidemiology , Female , Gestational Age , Humans , Oxidative Stress , Oxygen Radical Absorbance Capacity , Pregnancy , Pregnancy-Associated Plasma Protein-A/metabolism , Prenatal Diagnosis , Reactive Oxygen Species/metabolism , S-Nitrosothiols/blood , Ultrasonography
15.
Ginekol Pol ; 88(2): 87-95, 2017.
Article in English | MEDLINE | ID: mdl-28326518

ABSTRACT

OBJECTIVES: SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11-13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. MATERIAL AND METHODS: The study included 76 patients at 11-13 (+ 6d) gestational weeks, monitored throughout preg-nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. RESULTS: A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. CONCLUSIONS: The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11-13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.


Subject(s)
Birth Weight , Chorion/diagnostic imaging , Placenta Growth Factor/blood , Adult , Chorion/pathology , Chorionic Gonadotropin, beta Subunit, Human/blood , Female , Fetal Weight , Humans , Infant, Newborn , Infant, Small for Gestational Age , Organ Size , Pregnancy , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/metabolism , Risk Assessment , Ultrasonography, Prenatal , Young Adult
16.
Cell Mol Life Sci ; 72(23): 4613-32, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26070304

ABSTRACT

Patients suffering from tauopathies including frontotemporal dementia (FTD) and Alzheimer's disease (AD) present with intra-neuronal aggregation of microtubule-associated protein Tau. During the disease process, Tau undergoes excessive phosphorylation, dissociates from microtubules and aggregates into insoluble neurofibrillary tangles (NFTs), accumulating in the soma. While many aspects of the disease pathology have been replicated in transgenic mouse models, a region-specific non-transgenic expression model is missing. Complementing existing models, we here report a novel region-specific approach to modelling Tau pathology. Local co-administration of the pore-former polymeric 1,3-alkylpyridinium salts (Poly-APS) extracted from marine sponges, and synthetic full-length 4R recombinant human Tau (hTau) was performed in vitro and in vivo. At low doses, Poly-APS was non-toxic and cultured cells exposed to Poly-APS (0.5 µg/ml) and hTau (1 µg/ml; ~22 µM) had normal input resistance, resting-state membrane potentials and Ca(2+) transients induced either by glutamate or KCl, as did cells exposed to a low concentration of the phosphatase inhibitor Okadaic acid (OA; 1 nM, 24 h). Combined hTau loading and phosphatase inhibition resulted in a collapse of the membrane potential, suppressed excitation and diminished glutamate and KCl-stimulated Ca(2+) transients. Stereotaxic infusions of Poly-APS (0.005 µg/ml) and hTau (1 µg/ml) bilaterally into the dorsal hippocampus at multiple sites resulted in hTau loading of neurons in rats. A separate cohort received an additional 7-day minipump infusion of OA (1.2 nM) intrahippocampally. When tested 2 weeks after surgery, rats treated with Poly-APS+hTau+OA presented with subtle learning deficits, but were also impaired in cognitive flexibility and recall. Hippocampal plasticity recorded from slices ex vivo was diminished in Poly-APS+hTau+OA subjects, but not in other treatment groups. Histological sections confirmed the intracellular accumulation of hTau in CA1 pyramidal cells and along their processes; phosphorylated Tau was present only within somata. This study demonstrates that cognitive, physiological and pathological symptoms reminiscent of tauopathies can be induced following non-mutant hTau delivery into CA1 in rats, but functional consequences hinge on increased Tau phosphorylation. Collectively, these data validate a novel model of locally infused recombinant hTau protein as an inducer of Tau pathology in the hippocampus of normal rats; future studies will provide insights into the pathological spread and maturation of Tau pathology.


Subject(s)
Hippocampus/cytology , Neuronal Plasticity/physiology , Neurons/drug effects , Polymers/administration & dosage , Pyridinium Compounds/administration & dosage , tau Proteins/pharmacology , Animals , Behavior, Animal/drug effects , Calcium Signaling/drug effects , Cells, Cultured , Disease Models, Animal , Electrophysiology/methods , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Learning Disabilities/drug therapy , Male , Neurons/metabolism , Neurons/physiology , Phosphorylation , Polymers/pharmacology , Pyridinium Compounds/pharmacology , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Tauopathies/metabolism , tau Proteins/administration & dosage , tau Proteins/metabolism
17.
Clin Physiol Funct Imaging ; 34(3): 191-8, 2014 May.
Article in English | MEDLINE | ID: mdl-23981070

ABSTRACT

A brief Valsalva manoeuvre, lasting 2-3 s, performed by young healthy men during strength exercise reduces transmural pressure acting on intrathoracic arteries. In this study, we sought to verify this finding in older men. Twenty normotensive, prehypertensive and moderately hypertensive otherwise healthy men 46-69 years old performed knee extensions combined with inspiration or with brief Valsalva manoeuvre performed at 10, 20 and 40 mmHg mouth pressure. Same respiratory manoeuvres were also performed at rest. Non-invasively measured blood pressure, knee angle, respiratory airflow and mouth pressure were continuously registered. In comparison to inspiration, estimated transmural pressure acting on thoracic arteries changed slightly and insignificantly during brief Valsalva manoeuvre at 10 and 20 mmHg mouth pressure. At 40 mmHg mouth pressure, transmural pressure declined at rest (-8·8 ± 11·4 mmHg) and during knee extension (-12·1 ± 11·9 mmHg). This decline ensued, as peak systolic pressure increase caused by this manoeuvre, was distinctly <40 mmHg. Only a main effect of mouth pressure was revealed (P<0·001) and neither exercise nor interaction between these factors, what suggests that transmural pressure decline, depended mainly on intrathoracic pressure developed during brief Valsalva manoeuvre. Resting blood pressure did not influence the effect of brief Valsalva manoeuvre on transmural pressure.


Subject(s)
Aging , Blood Pressure , Hypertension/physiopathology , Muscle, Skeletal/physiopathology , Resistance Training , Thoracic Arteries/physiopathology , Valsalva Maneuver , Age Factors , Aged , Humans , Male , Middle Aged , Muscle Contraction , Muscle Strength , Prehypertension/physiopathology , Respiration , Sex Factors , Time Factors
18.
Arch Med Sci ; 10(6): 1078-85, 2014 Dec 22.
Article in English | MEDLINE | ID: mdl-25624842

ABSTRACT

INTRODUCTION: Our aim was to evaluate the differences in the early hemodynamic response to the tilt test (HUTT) in patients with and without syncope using impedance cardiography (ICG). MATERIAL AND METHODS: One hundred twenty-six patients (72 female/48 male; 37 ±17 years) were divided into a group with syncope (HUTT(+), n = 45 patients) and a group without syncope (HUTT(-), n = 81 patients). ECG and ICG signals were continuously recorded during the whole examination, allowing the calculation of heart rate (HR), stroke volume (SV), and cardiac output (CO) for every beat. The hemodynamic parameters (averaged over 1 min) were analyzed at the following points of the HUTT: the last minute of resting, the period immediately after the tilt (0 min), 1 min and 5 min after the maneuver. The absolute changes of HR, SV and CO were calculated for 0, 1, and 5 min after the maneuver in relation to the values at rest (ΔHR, ΔSV, ΔCO). Also, the percentage changes were calculated (HRi, SVi, COi). RESULTS: There were no differences between the groups in absolute and percentage changes of hemodynamic parameters immediately after and 1 min after tilting. Significant differences between the HUTT(+) and HUTT(-) groups were observed in the 5(th) min of tilting: for ΔSV (-27.2 ±21.2 ml vs. -9.7 ±27.2 ml; p = 0.03), ΔCO (-1.78 ±1.62 l/min vs. -0.34 ±2.48 l/min; p = 0.032), COi (-30 ±28% vs. -0.2 ±58%; p = 0.034). CONCLUSIONS: In the 5(th) min the decrease of hemodynamic parameters (ΔSV, ΔCO, COi) was significantly more pronounced in HUTT(+) patients in comparison to the HUTT(-) group.

19.
Cardiol J ; 20(1): 17-24, 2013.
Article in English | MEDLINE | ID: mdl-23558806

ABSTRACT

BACKGROUND: Little is known about the influence of aerobic training on the neurohormonal and hemodynamic responses to head-up tilt (HUT) and on autonomic balance at rest and after exercise in optimally treated, low risk post-coronary artery bypass grafting (CABG) patients. METHODS: One hundred male patients, mean age 56 ± 6 years, 3 months after CABG, were randomized to either 6-week training on cycloergometer, 3 times a week, at 70-80% of max tolerated heart rate (HR) (training group, n = 50) or to a control group (n = 50). At baseline and at the end of the study, all patients underwent: (1) cardiopulmonary exercise test with HR recovery (HRR) assessment; (2) 60% HUT during which HR, blood pressure (BP), stroke volume (SV by impedance cardiography) were monitored and blood samples were taken for determination of plasma catecholamines and ANP levels, and plasma renin activity; (3) assessment of HR variability (HRV) in the time and frequency domains at rest. RESULTS: During the final tests, HUT-induced changes in HR, BP, SV, cardiac output, total peripheral resistance, and noradrenaline were significantly lower in training group than in controls. In addition, after training faster post-exercise HRR, increased SDNN and a tendency towards an increase in the high frequency HRV power spectrum were found. CONCLUSIONS: Aerobic training improved neurohormonal and hemodynamic responses to head-up tilt test and favorably modified sympatho-vagal balance in low risk post-CABG patients.


Subject(s)
Autonomic Nervous System/physiology , Coronary Artery Bypass/rehabilitation , Exercise/physiology , Hemodynamics/physiology , Blood Pressure/physiology , Coronary Artery Disease/physiopathology , Coronary Artery Disease/rehabilitation , Coronary Artery Disease/surgery , Exercise Test , Exercise Tolerance/physiology , Heart Rate/physiology , Humans , Male , Middle Aged , Neurotransmitter Agents/physiology , Rest/physiology , Stroke Volume/physiology , Tilt-Table Test , Treatment Outcome
20.
Cardiol J ; 19(5): 550-6, 2012.
Article in English | MEDLINE | ID: mdl-23042327

ABSTRACT

The aim of this paper is the presentation of recent advancements in impedance cardiography regarding methodical approach, applied equipment and clinical or research implementations. The review is limited to the papers which were published over last 17 months (dated 2011 and 2012) in well recognised scientific journals.


Subject(s)
Cardiography, Impedance , Cardiovascular Diseases/diagnosis , Stroke Volume , Animals , Cardiography, Impedance/history , Cardiography, Impedance/trends , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/therapy , History, 21st Century , Humans , Models, Cardiovascular , Predictive Value of Tests
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