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1.
Poult Sci ; 102(3): 102452, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36621095

ABSTRACT

The profitability of pheasants breeding is influenced by many factors, but eggs quality is considered as the backbone for successful pheasant breeding. The objective of this study was to determine and compare various quality characteristics (physical, morphological, and mechanical) of eggs from three pheasant subspecies: common pheasant (Phasianus colchicus colchicus), Mongolian pheasant (Phasianus colchicus mongolicus), and black pheasant (Phasianus colchicus vs. tenebrosus). A total sample of 180 eggs (60 eggs of each pheasant subspecies) was collected from pheasant hens kept in aviaries in their first year of production (43-47 wk of age). The average weight and volume of eggs from common pheasants was significantly lower (P ˂ 0.05) than those from Mongolian and black pheasants. No significant differences between three pheasant subspecies were observed in albumen and yolk weight and percentage, while egg shell weight and percentage were significantly higher (P < 0.01) at eggs from black pheasants. In comparison to eggs from Mongolian and common pheasants, eggs from black pheasants had the thickest shell and the highest shell strength and required highest force to egg breaking. The values of breaking force and other mechanical characteristics depend on the direction of the loading force during egg compression. The data obtained by evaluating certain characteristics of egg quality can be useful to breeders when choosing a pheasant subspecies, as well as for choosing quality eggs for hatching and their storage.


Subject(s)
Eggs , Quail , Animals , Female , Ovum
2.
Clin Mol Allergy ; 15: 7, 2017.
Article in English | MEDLINE | ID: mdl-28392751

ABSTRACT

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy). METHODS: 7-18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up. RESULTS: There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation. CONCLUSIONS: Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.

3.
Neuroscience ; 236: 47-54, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23352936

ABSTRACT

The hippocampus plays a central role in stress-related mood disorders. The effects of acute vs. chronic stress on the integrity of hippocampal circuitry in influencing the vulnerability to, or resiliency against, neuronal injury are poorly understood. Here we investigated whether acute vs. chronic psychosocial isolation stress or a combination of the two (chronic stress followed by acute stress) influences the expression of the interneuronal marker parvalbumin (PV) and the chaperone-inducible heat shock protein 70 (Hsp70i) in different subregions of the hippocampus. Low levels of the Ca(2+)-binding protein (PV) may increase the vulnerability to neuronal injury, and Hsp70i represents an indicator of intense excitation-induced neuronal stress. Adult male Wistar rats were exposed to 2h of immobilization (IM) or cold (4°C) (acute stressors), 21d of social isolation (chronic stress), or a combination of both acute and chronic stress. Both chronic isolation and the combined stressors strongly decreased the PV-immunoreactive cells in the CA1, CA3 and dentate gyrus (DG) region of the hippocampus, while acute stress did not affect PV expression. The combination of acute and chronic stress induced a dramatic increase in Hsp70i expression in the DG, but Hsp70i expression was unaffected in acute and chronic stress alone. We also monitored serum corticosterone (CORT) levels as a neuroendocrine marker of the stress response. Acute stress increased CORT levels, while chronic isolation stress compromised hypothalamic-pituitary-adrenocortical (HPA) axis activity such that the normal stress response was impaired following subsequent acute stress. These results indicate that in contrast to acute stress, chronic isolation compromises the HPA axis and generates a considerable reduction in PV expression, representing a decrease in the calcium-buffering capacity and a putatively higher vulnerability of specific hippocampal interneurons to excitotoxic injury. The induction of Hsp70i expression in response to acute and chronic isolation reveals that neurons in the DG are particularly vulnerable to an acute stressor following a chronic perturbation of HPA activity.


Subject(s)
HSP72 Heat-Shock Proteins/biosynthesis , Hippocampus/metabolism , Parvalbumins/biosynthesis , Stress, Psychological/metabolism , Animals , Corticosterone/blood , Enzyme-Linked Immunosorbent Assay , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Immunohistochemistry , Male , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/physiopathology , Rats , Rats, Wistar , Social Isolation , Stress, Psychological/complications , Stress, Psychological/physiopathology
4.
Behav Brain Res ; 241: 27-31, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23228523

ABSTRACT

Glutamatergic mechanisms regulate neuronal circuits implicated in mood and anxiety. Emotional disorders as anxiety and depression are particularly difficult to treat during aging and mechanisms underlying emotional disturbances in the brain of the elderly are poorly understood. This may result from the small number of studies investigating these disorders in aged animals. Among glutamate receptors, metabotropic mGlu5 receptors are thought to play an important role, since their pharmacological blockade induces strong anxiolytic effects. However, the implication of mGlu5 in regulating anxiety is not yet completely understood. Here we analyzed both young adult and aged mice lacking mGlu5 receptors, to clarify, if genetic deletion of the receptor induces similar to pharmacological blockade anxiolytic effects. Unexpectedly, mGlu5 receptor knockout (KO) mice showed increased anxiety accentuating with aging. In contrast, young adult mice displayed an anti-depressive-like phenotype that was no longer detectable in aged animals. Our data support important distinct roles of mGlu5 receptors in modulating anxiety and depression during aging.


Subject(s)
Aging/metabolism , Anxiety/metabolism , Behavior, Animal/physiology , Receptors, Metabotropic Glutamate/metabolism , Age Factors , Aging/genetics , Aging/psychology , Animals , Anxiety/genetics , Anxiety/psychology , Mice , Mice, Knockout , Motor Activity/physiology , Receptor, Metabotropic Glutamate 5 , Receptors, Metabotropic Glutamate/genetics
5.
Neuroscience ; 223: 238-45, 2012 Oct 25.
Article in English | MEDLINE | ID: mdl-22885231

ABSTRACT

Mitochondrial dysfunction has been implicated in several psychiatric disorders, including depression. Given that the B-cell-lymphoma 2 (Bcl-2) protein family plays a role in the regulation of mitochondrial apoptotic pathway, we hypothesized that ratio of proapoptotic to antiapoptotic proteins (e.g., Bcl-2-associated X protein (Bax)/Bcl-2) may determine prosurvival/proapoptotic intracellular signaling under stress. We tested this hypothesis by examining the effects of 2h of acute stress immobilization (IM) or cold (C), 21days of social isolation as chronic stress and combined stress (chronic stress followed by acute stress) on cytosolic/mitochondrial levels and ratios of Bax and Bcl-2 proteins in relation to cytosolic nitric oxide (NO) metabolites (nitrates and nitrites) and p53 protein redistribution between cytosolic and mitochondrial compartments in the prefrontal cortex (PFC) and hippocampus (HIPP) of male Wistar rats. The stress-induced changes in serum corticosterone (CORT) concentrations were also followed. Acute stressors resulting in an elevated CORT level did not change the Bax/Bcl-2 ratio in either brain region. However, chronic isolation, resulting in CORT levels similar to basal values, led to a translocation of mitochondrial Bcl-2 to the cytosol in the PFC. Furthermore, the Bax/Bcl-2 ratio in the PFC was significantly increased following chronic isolation and remained elevated after combined stressors. NO metabolites were increased by chronic isolation and the two combined stressors in the HIPP and following the combined stressors in the PFC. Translocation of p53 and proapoptotic Bax from the cytosol into mitochondria in response to NO overproduction following combined stressors was detected only in the PFC. These data indicate that chronic isolation stress exerts opposing actions on p53 and NO mechanisms in a tissue-specific manner (PFC vs. HIPP), triggering proapoptotic signaling via Bcl-2 translocation in the PFC.


Subject(s)
Brain/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/physiology , Social Isolation/psychology , Stress, Psychological/pathology , bcl-2-Associated X Protein/metabolism , Analysis of Variance , Animals , Brain/pathology , Brain/ultrastructure , Corticosterone/blood , Cytosol/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation/physiology , Male , Mitochondria/metabolism , Nitrites/metabolism , Rats , Rats, Wistar , Stress, Psychological/blood , Tumor Suppressor Protein p53/metabolism
6.
Physiol Res ; 60(Suppl 1): S147-54, 2011.
Article in English | MEDLINE | ID: mdl-21777031

ABSTRACT

Many stress conditions are accompanied by skeletal muscle dysfunction and regeneration, which is essentially a recapitulation of the embryonic development. However, regeneration usually occurs under conditions of hypothalamus-pituitary-adrenal gland axis activation and therefore increased glucocorticoid (GC) levels. Glucocorticoid receptor (GR), the main determinant of cellular responsiveness to GCs, exists in two isoforms (GRalpha and GRbeta) in humans. While the role of GRalpha is well characterized, GRbeta remains an elusive player in GC signalling. To elucidate basic characteristics of GC signalling in the regenerating human skeletal muscle we assessed GRalpha and GRbeta expression pattern in cultured human myoblasts and myotubes and their response to 24-hour dexamethasone (DEX) treatment. There was no difference in GRalpha mRNA and protein expression or DEX-mediated GRalpha down-regulation in myoblasts and myotubes. GRbeta mRNA level was very low in myoblasts and remained unaffected by differentiation and/or DEX. GRbeta protein could not be detected. These results indicate that response to GCs is established very early during human skeletal muscle regeneration and that it remains practically unchanged before innervation is established. Very low GRbeta mRNA expression and inability to detect GRbeta protein suggests that GRbeta is not a major player in the early stages of human skeletal muscle regeneration.


Subject(s)
Cell Proliferation , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Myoblasts, Skeletal/metabolism , Receptors, Glucocorticoid/metabolism , Regeneration , Cell Proliferation/drug effects , Cells, Cultured , Dexamethasone/pharmacology , Gene Expression Regulation , Humans , Muscle Fibers, Skeletal/drug effects , Muscle, Skeletal/cytology , Muscle, Skeletal/drug effects , Myoblasts, Skeletal/drug effects , RNA, Messenger/metabolism , Receptors, Glucocorticoid/agonists , Receptors, Glucocorticoid/genetics , Regeneration/drug effects , Time Factors
7.
J Neurosci Res ; 89(9): 1461-70, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21656845

ABSTRACT

Mitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase-3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors. Mitochondrial p53 can suppress the antioxidant enzyme MnSOD, so its activity was also determined. In the prefrontal cortex, but not in hippocampus, increased protein levels of p53 were found in mitochondria, leading to cytochrome c release into cytoplasm, activation of caspase-3, and apoptotic cell death following combined stressors. Decreased mitochondrial MnSOD activity following combined stressors in both brain structures indicated a state of oxidative stress. This suggests that chronic isolation stress compromises mitochondrial MnSOD activity in both the prefrontal cortex and the hippocampus but likely results in mitochondrial-triggered proapoptotic signaling mediated by a transcription-independent p53 mechanism only in the prefrontal cortex. Thus, our data demonstrate a tissue-specific (prefrontal cortex vs. hippocampus) response to applied stressors.


Subject(s)
Caspase 3/metabolism , Cytochromes c/metabolism , Mitochondria/metabolism , Stress, Psychological/metabolism , Tumor Suppressor Protein p53/metabolism , Analysis of Variance , Animals , Apoptosis/physiology , Chronic Disease , Corticosterone/blood , Disease Models, Animal , Frontal Lobe/metabolism , Hippocampus/metabolism , Male , Prefrontal Cortex/metabolism , Rats , Rats, Wistar , Social Isolation , Superoxide Dismutase/metabolism , Tissue Distribution
8.
Appl Radiat Isot ; 67(11): 2062-7, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19700332

ABSTRACT

Air-ions and radon are two atmospheric trace constituents which have two opposite effects on human health: the ions are beneficial, and radon gas is potentially lethal as it increases the risk of lung cancer. In the lower troposphere, radon is the most important generator of the air-ions. Ionization by cosmic rays and radioactive minerals is almost constant in daily cycles, and variation of air-ion concentrations is attributed to changes of the radon activity. Air-ion and radon concentrations in outdoor and indoor space and their vertical gradients in residential buildings were measured. Gerdien type air-ion detector "CDI-06" made in our laboratory and radon monitor "RAD7" were utilized for these measurements. Correlation coefficient between positive air-ion and Rn indoor concentrations was approximately 0.7. Outdoor and indoor peak values were simultaneous while vertical gradient of concentrations in indoor measurements was evident. The indoor experiments showed that positive air-ion concentration could be an alternative method of radon activity concentration evaluation.


Subject(s)
Air Pollutants, Radioactive/analysis , Air Pollution, Indoor/analysis , Environmental Exposure/analysis , Radiation Monitoring/methods , Radon/analysis , Radiation Dosage , Serbia
9.
Physiol Res ; 57(2): 205-213, 2008.
Article in English | MEDLINE | ID: mdl-17552876

ABSTRACT

The aim of the present study was to define the stress-induced pattern of cytosolic glucocorticoid receptor (GR) and Hsp70 protein in the liver of male Wistar rats exposed to different stress models: acute (2 h/day) immobilization or cold (4 degrees C); chronic (21 days) isolation, crowding, swimming or isolation plus swimming and combined (chronic plus acute stress). Changes in plasma levels of corticosterone were studied by radioimmunoassay (RIA). The results obtained by Western immunoblotting showed that both acute stressors led to a significant decrease in cytosolic GR and Hsp70 levels. Compared to acute stress effects, only a weak decrease in the levels of GR and Hsp70 was demonstrated in chronic stress models. Chronically stressed rats, which were subsequently exposed to novel acute stressors (immobilization or cold), showed a lower extent of GR down-regulation when compared to acute stress. The exception was swimming, which partially restores this down-regulation. The observed changes in the levels of these major stress-related cellular proteins in liver cytosol lead to the conclusion that chronic stressors compromise intracellular GR down-regulation in the liver.


Subject(s)
Corticosterone/blood , HSP70 Heat-Shock Proteins/metabolism , Liver/metabolism , Receptors, Glucocorticoid/metabolism , Stress, Psychological/metabolism , Adaptation, Physiological , Analysis of Variance , Animals , Chronic Disease , Cold Temperature , Disease Models, Animal , Gene Expression Regulation/physiology , Immobilization , Male , Random Allocation , Rats , Rats, Wistar
10.
Appl Ergon ; 34(1): 45-9, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12523804

ABSTRACT

The paper presents research results of the vibration transmitted from the steering wheel of the small tractor with a 4-wheel drive to the driver's hands. The vibration measurements were carried out on the tractor randomly chosen from the producer's store-house. Before testing the tractor was examined and adjusted following the producer's recommendations. The vibration levels were measured at idling and at full load. The vibration level on the steering wheel was measured and analyzed and the frequency spectra for the chosen working conditions were obtained. The frequency-weighted acceleration, given in m/s(-2), was calculated. The vibration total value was defined as the root-mean-square of the three component values. The obtained values are graphically represented in accordance with ISO/DIS 5349-1979 and ISO5349-1-2001. The vibration exposure for the predicted 10% prevalance of vibration-induced white finger in accordance with Annex C of the same standard was also tested.


Subject(s)
Motor Vehicles , Vibration , Acceleration , Humans , Occupational Health
11.
Med Pregl ; 54(11-12): 539-42, 2001.
Article in Croatian | MEDLINE | ID: mdl-11921687

ABSTRACT

INTRODUCTION: Otoacoustic emission is a phenomenon that may occur in a large group of normal-hearing subjects. Ear is an organ which collects and treats sounds from the surrounding environment, and nerve fibres transmit the perceived information to the brain in terms of nerve signals. However, ear can also produce a sound (otoacoustic-emission), which can be recorded using very sensitive microphones placed in the ear canal. OTOACOUSTIC EMISSION: Otoacoustic emissions may be spontaneous (SOAE) or may be a response to given auditory stimuli: transiently evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Applications of otoacoustic emissions in clinical and experimental medicine are various. Hearing screening program of newborns aims to identify infants with permanent bilateral hearing loss in the first days after birth. Screening programs are based on recordings of transiently evoked otoacoustic emissions (TEOAE) in the first step, and then (if it is necessary) brainstem evoked response audiometry. Transiently evoked otoacoustic emissions may also be used for differential diagnosis of cochlear and retrocochlear disorder. UTILIZATION: In cases of substantial retrocochlear pathological findings without cochlear involvement, transiently evoked otoacoustic emissions should be recordable because outer hair cell function is unaffected. It is possible to detect ototoxic effects of drugs before hearing loss can be detected by other methods (pure-tone audiometry). In a similar way, using otoacoustic emissions, it is possible to detect noise induced damages of the outer hair cells. Otoacoustic emissions provide a unique means for assessing the integrity of the medial efferent pathway. Further research into the properties of various types of otoacoustic emissions would contribute to understanding of cochlear function, and in particular, the relative roles of inner and outer hair cells. Evoked otoacoustic emissions are directly related to outer hair cell function and may be somewhat independent of inner hair cells. At present, there is insufficient evidence to indicate whether inner and outer hair cell disorders can exist separately, and if they can, whether they are so strongly correlated that statistically the distinction is meaningless. Applications of otoacoustic emissions in clinical practice is an important route in furthering our understanding.


Subject(s)
Cochlea/physiology , Otoacoustic Emissions, Spontaneous/physiology , Hearing Disorders/diagnosis , Hearing Disorders/physiopathology , Humans
12.
Med Pregl ; 54(7-8): 332-7, 2001.
Article in Croatian | MEDLINE | ID: mdl-11905181

ABSTRACT

INTRODUCTION: Objective evaluation of hearing threshold and detection of hearing impairment are the basic prerequisites for hearing and speech rehabilitation. In infants and early pre-school children tonal audiometry is not possible. Though subjective, tonal audiometry is the most reliable method for evaluation of hearing threshold. Therefore, in children of this age, hearing threshold is evaluated by objective electroacoustic methods: early brainstem auditory evoked potentials (BAEP) and acoustic stapedius reflex. MATERIAL AND METHODS: In 60 adult examinees (120 ears) with normal hearing we analyzed the correlation between biological hearing threshold determined by tonal audiometry and threshold of ipsilateral stapedius reflex, as well as response threshold determined by brainstem evoked response audiometry (BERA). RESULTS AND DISCUSSION: We found a statistically significant correlation between biological hearing threshold and response threshold evaluated by brainstem evoked response audiometry. The linear Pearson correlation coefficient of: r = 0.40 for 500 Hz, r = 0.41 for 1,000 Hz, r = 0.44 for 2,000 Hz and r = 0.43 for 4,000 Hz (p < 0.01 for all values). Correlation coefficients between the biological hearing threshold and ipsilateral stapedius reflex threshold were not significant for 500 Hz (r = 0.46) and 1,000 Hz (r = 0.082), negative correlation was found for 2,000 Hz (r = 0.2656, p < 0.05) and significant correlation was confirmed only for 4,000 Hz (r = 0.225, p < 0.05). CONCLUSION: In regard to evident reliability of objective evaluation of hearing threshold by brainstem evoked response audiometry, this paper also suggests correction factors for evaluation of biological hearing threshold, and lists the deficiencies of hearing threshold assessment by this--still most accurate electrophysiological method.


Subject(s)
Auditory Threshold , Evoked Potentials, Auditory, Brain Stem , Hearing Tests , Reflex, Acoustic , Adult , Female , Humans , Male
13.
Med Pregl ; 54(5-6): 267-72, 2001.
Article in Croatian | MEDLINE | ID: mdl-11759224

ABSTRACT

INTRODUCTION: Noise is one of the commonest environmental pollutants and it is defined as a sound which bothers, irritates, which is unpleasant and can damage hearing. The degree of negative effects of noise depends on its intensity, spectrum of frequency, nature, duration of exposition and individual sensibility. PURPOSE: This work is supposed to establish the degree of correlation between hearing damage and professional exposition to one of physical stressors of work environment--noise. MATERIAL AND METHODS: Investigation regarding work conditions included intensity and frequency analysis of noise at workplaces. The examination sample included 101 workers of "NIS--Naftagas" section "Hidrosonda" employed as drilling workers. The control group consisted of 50 workers not exposed to noise or any other professional influences, like workers from the examination sample. RESULTS: The results on the observed workplaces show that noise is of high intensity and bad frequency spectrum. Exposition of workers to noise is a highly important factor for hearing damages (p = 0.002). The relative risk for hearing damage is four times greater in relation to the control group (odds ratio 4.1). Attributable fraction (preventive potential) of noise factor is 61%. Smoking associated with exposition to noise multiplies the risk of hearing damage (odds ratio 5.8) while with non-smokers the risk decreases (odds ratio 3.0). DISCUSSION: Professional hearing disorders occur slowly and increase with time spent at noisy workplaces. At the beginning it presents with buzzing in ears and dizziness followed by latent phase after which hearing disorders occur. Tone audiometry is used to register first signs of hearing loss, whereas manifestations in social contacts come later. CONCLUSION: Once diagnosed hearing disorders cannot be cured so a lot more care should be paid to this problem. It is necessary to provide adequate work conditions by applying appropriate technologies, tools, work organisation, personal protection equipment, as well as previous and periodical examinations of hearing by tone audiometry before employing workers and during their work in noisy conditions.


Subject(s)
Hearing Loss, Noise-Induced/diagnosis , Noise, Occupational/adverse effects , Adult , Auditory Threshold , Hearing Loss, Noise-Induced/etiology , Hearing Loss, Noise-Induced/physiopathology , Humans , Male , Middle Aged , Occupations , Risk Factors , Smoking/adverse effects
14.
Med Pregl ; 54(9-10): 423-31, 2001.
Article in English, Croatian | MEDLINE | ID: mdl-11876003

ABSTRACT

Due to increasing number of patients, reduced possibilities of diagnostics and therapy as well as poor living conditions as a result of total socio-political and economic situation in our country in the last ten years, health workers have been exposed to additional stress factors. Therefore, we wonted to establish to what extent professional stress affects appearance of complications in arterial hypertension with health workers. The examination included employees treated in the health centers "Hospital" and "Novi Sad". According to register for chronic mass non-contagious diseases of MONICA Project, younger patients suffering from arterial hypertension were excluded. From the aspect of possible causative factors of occupation on appearance of cardiovascular complications in patients already suffering from arterial hypertension, the examined group involved doctors and nurses. The control group included laboratory technicians, clerks, cleaners and service workers. It was established that doctors and nurses with hypertension registered in earlier life periods, were more vulnerable to angina pectoris, myocardial infarction and cerebrovascular insult as complications, compared to the rest of employees (if age as a risk factor is excluded) (RR = 3.7; 95% confidence interval 1.6 < RR < 8.6).


Subject(s)
Cardiovascular Diseases/etiology , Health Personnel , Medical Staff, Hospital/psychology , Occupational Diseases/psychology , Stress, Psychological/etiology , Adult , Female , Humans , Hypertension/complications , Male , Middle Aged , Nurses , Physicians
15.
Am J Physiol ; 277(3): F428-36, 1999 09.
Article in English | MEDLINE | ID: mdl-10484526

ABSTRACT

Oxidant-induced cell injury has been implicated in the pathogenesis of several forms of acute renal failure. The present studies examined whether activation of poly(ADP-ribose)polymerase (PARP) by oxidant-induced DNA damage contributes to oxidant injury of renal epithelial cells. H2O2 exposure resulted in an increase in PARP activity and decreases in cell ATP and NAD content. These changes were significantly inhibited by 10 mM 3-aminobenzamide (3-ABA), a PARP inhibitor. In contrast, H2O2-induced DNA damage was not prevented by 3-ABA. Exposure of LLC-PK(1) cells to 1 mM H2O2 for 2 h induced necrotic cell death as measured by increased lactate dehydrogenase (LDH) release. 3-ABA completely prevented the H2O2-induced LDH release. Live/dead fluorescent staining confirmed the protection by 3-ABA. These results are consistent with the view that oxidant-induced DNA damage activates PARP and that the subsequent ATP and NAD depletion contribute to necrotic cell death. Of note, although protected from necrosis, cells treated with H2O2 and 3-ABA underwent apoptosis as evidenced by DNA fragmentation and bis-benzimide staining. In conclusion, activation of PARP contributes to oxidant-induced ATP depletion and necrosis in LLC-PK1 cells. However, PARP inhibition may target cells toward an apoptotic form of cell death.


Subject(s)
Apoptosis/physiology , Kidney Tubules, Proximal/pathology , Kidney Tubules, Proximal/physiology , Poly(ADP-ribose) Polymerases/physiology , Animals , Apoptosis/drug effects , Benzamides/pharmacology , DNA Damage/drug effects , Enzyme Inhibitors/pharmacology , LLC-PK1 Cells , Necrosis , Oxidants/toxicity , Poly(ADP-ribose) Polymerase Inhibitors , Swine
16.
Med Pregl ; 52(9-10): 343-50, 1999.
Article in Croatian | MEDLINE | ID: mdl-10624382

ABSTRACT

INTRODUCTION: This paper deals with basic rational antiepileptic therapeutic procedures in children with special consideration of numerous specificities which occur in childhood: difficulties in establishing correct syndrome diagnosis, predominantly after the first or first few seizures which makes it difficult to decide about appropriate syndrome-specific therapy in regard to efficacy, mechanism of action and range of antiepileptic action; difficulties in assessment of subjective factors (their adverse effects and recognition of seizures with subjective symptoms), children's vulnerability in regard to drug toxicity; age-specific pharmacokinetics of these drugs. MATERIAL AND METHODS: The number of available antiepileptics today is great due to new drugs, but carbamazepine (CBZ) and valproate (VAL) are still basic antiepileptics, although carbamazepine's action is reduced to partial epilepsies. The paper describes range of action of available antiepileptics in regard to classification of epileptic seizures and most frequent epileptic syndromes. DISCUSSION: Adverse effects of antiepileptic agents depend on the age, so examples of age-dependent adverse effects are given considering conventional and new antiepileptics. It is well known that optimal control of seizures depends not only on correct choice of drug, but also on appropriate dosage; it is necessary to be informed about age-dependent characteristics of clinical pharmacokinetics: resorption, metabolism, elimination and half-life of antiepileptics. Although 70-80% of children may be well treated with monotherapy, 15% of children require combination of 2 or more drugs causing drug interactions in resorption, distribution, metabolism and elimination. Examples of antiepileptic interactions as well as interactions of other drugs and antiepileptics are given. The paper also deals with special importance of the psychosocial aspects of epilepsy. These children are often unaccepted by others, mostly because others are afraid of their disease, which contributes to poor quality of life of these children. Development of intellectual, emotional functions, physical development and socialization, apart from affecting the choice of drug, make epilepsy treatment in children more complex, with special emphasis on mental-hygienic aspects of complete management of children. CONCLUSION: Only a complex approach to child suffering from epilepsy may provide optimal development, quality of life improvement and complete social integration. Rational therapy of epilepsy in children requires good knowledge not only of age-specific syndromes, clinical pharmacology of anticonvulsants, their efficacy and range of action, but also specificity of their metabolism in children, profile of adverse effects as well as facing numerous nonmedical problems.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Anticonvulsants/adverse effects , Child , Humans
17.
Am J Physiol ; 274(6): F1070-7, 1998 06.
Article in English | MEDLINE | ID: mdl-9841498

ABSTRACT

Extracellular ATP affects a wide variety of cells via purinergic membrane receptors. One class of purinergic receptors, P2X, consists of ATP-gated, calcium-permeable, cation-selective channels. We performed whole cell patch-clamp studies, intracellular calcium concentration ([Ca2+]i) measurements, and reverse transcription-polymerase chain reaction (RT-PCR) to determine whether P2X receptors are expressed in LLC-PK1 cells. First, in patch-clamp studies, 100 microM ATP depolarized the cell membrane and increased the whole cell conductance of LLC-PK1 cells. This response was dose dependent and inhibited by 100 microM suramin, a P2 receptor antagonist. The ATP-induced conductance was cation selective but did not discriminate between Na+ and K+. ADP, alpha,beta-methylene-ATP, and beta,gamma-methylene-ATP had no effect on the whole cell conductance. Next, 10 microM ATP caused a rapid rise in [Ca2+]i in LLC-PK1 cells. This effect of ATP was inhibited by the absence of extracellular calcium and by suramin but not by pretreatment with pertussis toxin. ADP and beta,gamma-methylene-ATP had little or no effect on [Ca2+]i. Finally, RT-PCR produced a 330-bp fragment from LLC-PK1 cell RNA, whose sequence was 80% identical to the rat P2X1 receptor. We conclude that LLC-PK1 cells express purinergic receptors of the P2X class, which mediate depolarization and calcium entry when activated.


Subject(s)
Adenosine Triphosphate/pharmacology , Calcium/metabolism , Kidney Tubules, Proximal/metabolism , Receptors, Purinergic P2/drug effects , Amino Acid Sequence , Animals , Epithelial Cells/drug effects , Epithelial Cells/metabolism , LLC-PK1 Cells , Molecular Sequence Data , Rats , Receptors, Purinergic P2/metabolism , Suramin/pharmacology , Swine
18.
Med Pregl ; 51(7-8): 359-63, 1998.
Article in Croatian | MEDLINE | ID: mdl-9769673

ABSTRACT

This paper provides a brief biography of an outstanding physiologist and academician Petr Kuzmich Anokhin. With his functional system theory, academician P. K. Anokhin was the first to introduce a systematic approach to discussing functioning of an organism. Principles of functional systems have been applied in technical systems as well.


Subject(s)
History, 20th Century , Humans , Physiology/history , USSR
19.
Biochem Mol Biol Int ; 45(3): 545-54, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9679655

ABSTRACT

The activity of the isoenzymes of N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) is determined in the serum of insulin-dependent (IDDM) and non-insulin-dependent diabetics (NIDDM) with or without diabetic complications. The increase in total activity of serum NAG in diabetics is proportional to the A form activity (r = 0.976, p < 0.0001). The contribution of the A form activity (65.87 +/- 5.99%) to total NAG activity of IDDM and NIDDM diabetics with and without complications does not change considerably compared to the control group. The contribution of the B form activity depends on the state of metabolic monitoring and diabetic complications. A significantly lower activity of the serum B form was found in IDDM (p < 0.001) and NIDDM diabetics (p < 0.05) compared to the healthy individuals, as well as the higher activity ratios of the A/B forms. A decrease in serum B form is correlated with the occurrence and abundance of the intermediary I forms (r = 0.665). These changes are particularly significant in the individuals with the pronounced microangiopathy.


Subject(s)
Acetylglucosaminidase/blood , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 2/enzymology , Isoenzymes/blood , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Humans
20.
Vojnosanit Pregl ; 55(2 Suppl): 71-4, 1998.
Article in English | MEDLINE | ID: mdl-9623362

ABSTRACT

Two groups of 40 surgical Intensive Care Unit patients each, were included in the study. All patients had severe intraabdominal infections and sepsis, and septic score higher than 20. All were treated with individual specified conventional symptomatic therapy, and 40 of them received high doses of intravenous immunoglobulins. Significantly lower mortality rate was noticed in IVIG group (40%) than in control group (63.7%). Immunoglobulin therapy also decreased mortality rate in patients with septic shock, but it was no more effective than conventional therapy in patients with multiple organ failure (MOF).


Subject(s)
Abdomen , Bacterial Infections/therapy , Immunoglobulins, Intravenous/administration & dosage , Sepsis/therapy , Abdomen/surgery , Adult , Bacterial Infections/complications , Female , Humans , Male , Sepsis/complications
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