Pathophysiology (Pathophysiology)

Publications in this journal

• Article: Swedish review strengthens grounds for concluding that radiation from cellular and cordless phones is a probable human carcinogen.

  Devra Lee Davis, Santosh Kesari, Colin L Soskolne, Anthony B Miller, Yael Stein
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  ABSTRACT: With 5.9 billion reported users, mobile phones constitute a new, ubiquitous and rapidly growing exposure worldwide. Mobile phones are two-way microwave radios that also emit low levels of electromagnetic radiation. Inconsistent results have been published on potential risks of brain tumors tied with mobile phone use as a result of important methodological differences in study design and statistical power. Some studies have examined mobile phone users for periods of time that are too short to detect an increased risk of brain cancer, while others have misclassified exposures by placing those with exposures to microwave radiation from cordless phones in the control group, or failing to attribute such exposures in the cases. In 2011, the World Health Organization, International Agency for Research on Cancer (IARC) advised that electromagnetic radiation from mobile phone and other wireless devices constitutes a "possible human carcinogen," 2B. Recent analyses not considered in the IARC review that take into account these methodological shortcomings from a number of authors find that brain tumor risk is significantly elevated for those who have used mobile phones for at least a decade. Studies carried out in Sweden indicate that those who begin using either cordless or mobile phones regularly before age 20 have greater than a fourfold increased risk of ipsilateral glioma. Given that treatment for a single case of brain cancer can cost between $100,000 for radiation therapy alone and up to $1 million depending on drug costs, resources to address this illness are already in short supply and not universally available in either developing or developed countries. Significant additional shortages in oncology services are expected at the current growth of cancer. No other environmental carcinogen has produced evidence of an increased risk in just one decade. Empirical data have shown a difference in the dielectric properties of tissues as a function of age, mostly due to the higher water content in children's tissues. High resolution computerized models based on human imaging data suggest that children are indeed more susceptible to the effects of EMF exposure at microwave frequencies. If the increased brain cancer risk found in young users in these recent studies does apply at the global level, the gap between supply and demand for oncology services will continue to widen. Many nations, phone manufacturers, and expert groups, advise prevention in light of these concerns by taking the simple precaution of "distance" to minimize exposures to the brain and body. We note than brain cancer is the proverbial "tip of the iceberg"; the rest of the body is also showing effects other than cancers.
  Pathophysiology 05/2013;
• Article: Erythropoietin improves spatial learning and memory in streptozotocin model of dementia.

  Gholamali Hamidi, Zohreh Arabpour, Moloud Shabrang, Bahman Rashidi, Hojjatallah Alaei, Mohammad Reza Sharifi, Mahmoud Salami, Parham Reisi
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  ABSTRACT: Alzheimer's disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimer's disease. Rat model of Alzheimer's was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimer's. After that, they received erythropoietin (5000IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimer's disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.
  Pathophysiology 04/2013;
• Article: Garlic (Allium sativum) attenuate glomerular glycation in streptozotocin-induced diabetic rats: A possible role of insulin.

  Khaled K Al-Qattan, Martha Thomson, Muslim Ali, Mohamed H Mansour
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  ABSTRACT: Objective: This study investigated the effect of fresh garlic aqueous extract on glomerular glycation in streptozotocin-induced diabetic rats. Method: Serum insulin and glucose, in addition to renal corpuscles and erythrocyte hemoglobin glycation were determined in normal saline-treated normal rats (NS-NR), normal saline-treated diabetic rats (NS-DR) and garlic-treated diabetic rats (G-DR). Results: Compared to NS-NR, NS-DR showed significant decrease in serum insulin and increase in serum glucose and hemoglobin glycation. NS-DR also showed intense, diffused glomerular periodic acid Schiff activity. Compared to NS-DR, G-DR showed significant increase in serum insulin and decrease in serum glucose and hemoglobin glycation. Furthermore, the G-DR glomerular periodic acid Schiff activity and distribution was almost restored to that observed in NS-NR. Conclusion: Garlic may attenuate glomerular glycation in streptozotocin-induced diabetic rats. This effect could be partially mediated via euglycemia induced by revitalization of endogenous insulin.
  Pathophysiology 04/2013;
• Article: Body weight reduction and metformin: Roles in polycystic ovary syndrome.

  Omar Al-Nozha, Fawziah Habib, Moaz Mojaddidi, Mohamed Fath El-Bab
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  ABSTRACT: Background and objectives: Polycystic ovary syndrome (PCOS) is a common problem in women at fertile age. A prospective study was conducted to clarify the pathophysiological responses during an application of insulin sensitizer, metformin and weight reduction therapy at the Gynecology Center in Ohud hospital, in AL-Madinah AL-Munawarah, Kingdom of Saudi Arabia. Methodology: Twenty healthy women served as controls and 180 PCOS women divided into three groups participated in the study. First group was treated with Clomid citrate 100mg/day from the 2nd day of menses to the 6th day plus gonadotrophin from day three to the 13th. Group II was treated as group I plus 850mg metformin twice a day and group III was treated as group I plus weight reduction. Clinical symptoms, menstrual pattern, hirsutism, blood glucose, body mass index, waist-to-hip ratio, insulin, hormonal, and lipid profiles were assessed pre- and post treatment. Insulin resistance was calculated. Results: PCOS women had significantly higher values than the healthy women in most of the measurements. Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR. Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels. HOMA-IR was significantly higher in women with PCOS. HOMA-IR was positively correlated with testosterone, estradiol, TG, total cholesterol and LDL-cholesterol parameters, and negatively correlated with HDL-cholesterol and FSH levels. Conclusion: Metformin therapy and weight reduction had favorable influences on the basic metabolic and hormonal profiles in women with PCOS and that metformin and lifestyle modification (weight reduction via diet restriction or exercise) resulted in a significantly greater weight loss than hormonal therapy alone. Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.
  Pathophysiology 04/2013;
• Article: Electromagnetic hypersensitive Finns: Symptoms, perceived sources and treatments, a questionnaire study.

  M Hagström, J Auranen, R Ekman
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  ABSTRACT: The aim was to analyze the subjective experiences of Finns who describe themselves as suffering from electromagnetic hypersensitivity (EHS), their symptoms, self-perceived sources of the health complaints and the effectiveness of medical and complementary alternative therapies. A total of 395 questionnaires were mailed to self-diagnosed EHS persons. Of the participants 345 belonged to a Finnish self-help group and 50 came from outside of the group. The return rate of the study was 52.1% (206) and 80.9% of the respondents were women. Before the onset of EHS the most common health complaints were different types of allergies (35.1%, 68). During the acute phase of EHS the most common symptoms were nervous system related: "stress" (60.3%, 117), "sleeping disorders" (59.3%, 115) and "fatigue" (57.2%, 111). The sources that were most often reported to have triggered EHS were: "personal computers" (50.8%, 94) and "mobile phones" (47.0%, 87). The same devices were also claimed to cause the most symptoms during the acute phase. After the acute phase of EHS had passed, the respondents still claimed to react to these same digital and wireless devices while their reactions to basic electrical appliances were reduced. According to 76% of 157 respondents the reduction or avoidance of electromagnetic fields (EMF) helped in their full or partial recovery. The best treatments for EHS were given as: "dietary change" (69.4%), "nutritional supplements" (67.8%) and "increased physical exercise" (61.6%). The official treatment recommendations of psychotherapy (2.6%) and medication (-4.2%) were not significantly helpful. According to the present results the official treatment protocols should take better account the EHS person's own experiences. The avoidance of electromagnetic radiation and fields effectively removed or lessened the symptoms in EHS persons.
  Pathophysiology 04/2013;
• Article: Leukocyte infiltration in lung, muscle, and liver after limb compression in rats.

  Mauricio Wanderley Moral Sgarbi, Bomfim A Silva, Carmem Maldonado Peres, Tatiana Carolina Alba, Rui Curi, Francisco Garcia Soriano, Daniel Araki Ribeiro, Irineu Tadeu Velasco
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  ABSTRACT: Muscle crush injury is associated with systemic manifestations known as crush syndrome. A systemic inflammatory response syndrome may be triggered by isolated crush injury. Using myeloperoxidase (MPO) activity and plasma fatty acid composition, we investigated the inflammatory response in distant organs after isolated limb compression in rats. Male Wistar rats were submitted to 1h of hind limb compression by a latex ribbon. Myeloperoxidase activity was measured in muscle, liver, and lung at progressive times (1, 2 or 4h) after bandage release. Plasma fatty acid composition was evaluated as an indirect measure of oxidative stress. The liver and hind limb muscles showed a transient increase in MPO activity. Pulmonary MPO activity, otherwise, increased progressively throughout the study and reached statistically significant values at 4h when compared to all other groups (p<0.05). Plasma levels of unsaturated fatty acids decreased gradually after decompression (p<0.05 compared to controls after 4h). Blunt traumatic muscle compression was associated with rapid and transient muscle and liver inflammatory cell infiltration but otherwise, polymorphonuclear cells showed progressive aggregation in lungs. The plasmatic unsaturated index decreased throughout the 4h after muscle release. We demonstrated that limb compression was associated with oxidative stress and distant inflammatory responses. Progressive inflammatory cell infiltration in lungs could be related with the delayed systemic adverse responses found after crush injury.
  Pathophysiology 02/2013;
• Article: Mismatch between peripheral and central demands in salt-sensitive hypertensive Dahl rats.

  Yasuhiro Nishida, Megumi Tandai-Hiruma, Takehito Kemuriyama, Kohsuke Hagisawa
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  ABSTRACT: Sympathetic nerve activity in essential hypertension, which accounts for 90% of all hypertension cases, is in general thought to be elevated regardless of whether there is salt sensitivity or insensitivity. The cause is thought to be an abnormality in the sympathetic center. On the other hand, neuronal nitric oxide synthase-expressing neurons that function to inhibit the sympathetic center are clearly activated in the salt-sensitive hypertensive Dahl rat model. How is this related to sympathetic hyperactivity and hypertension? Also, how is hypertension associated with peripheral vessel contractility and renal function? Human life is supported by the body's various essential functions. The circulatory system links all these functions into one system that cannot be separated. Blood pressure is the driving force of this circulatory system, and both the central and peripheral demands determine the output. We examined the 'mismatch' between these two sides and its association with hypertension.
  Pathophysiology 01/2013;
• Article: Use of mobile phones and cordless phones is associated with increased risk for glioma and acoustic neuroma.

  Lennart Hardell, Michael Carlberg, Kjell Hansson Mild
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  ABSTRACT: The International Agency for Research on Cancer (IARC) at WHO evaluation of the carcinogenic effect of RF-EMF on humans took place during a 24-31 May 2011 meeting at Lyon in France. The Working Group consisted of 30 scientists and categorised the radiofrequency electromagnetic fields from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields (RF-EMF), as Group 2B, i.e., a 'possible', human carcinogen. The decision on mobile phones was based mainly on the Hardell group of studies from Sweden and the IARC Interphone study. We give an overview of current epidemiological evidence for an increased risk for brain tumours including a meta-analysis of the Hardell group and Interphone results for mobile phone use. Results for cordless phones are lacking in Interphone. The meta-analysis gave for glioma in the most exposed part of the brain, the temporal lobe, odds ratio (OR)=1.71, 95% confidence interval (CI)=1.04-2.81 in the ≥10 years (>10 years in the Hardell group) latency group. Ipsilateral mobile phone use ≥1640h in total gave OR=2.29, 95% CI=1.56-3.37. The results for meningioma were OR=1.25, 95% CI=0.31-4.98 and OR=1.35, 95% CI=0.81-2.23, respectively. Regarding acoustic neuroma ipsilateral mobile phone use in the latency group ≥10 years gave OR=1.81, 95% CI=0.73-4.45. For ipsilateral cumulative use ≥1640h OR=2.55, 95% CI=1.50-4.40 was obtained. Also use of cordless phones increased the risk for glioma and acoustic neuroma in the Hardell group studies. Survival of patients with glioma was analysed in the Hardell group studies yielding in the >10 years latency period hazard ratio (HR)=1.2, 95% CI=1.002-1.5 for use of wireless phones. This increased HR was based on results for astrocytoma WHO grade IV (glioblastoma multiforme). Decreased HR was found for low-grade astrocytoma, WHO grades I-II, which might be caused by RF-EMF exposure leading to tumour-associated symptoms and earlier detection and surgery with better prognosis. Some studies show increasing incidence of brain tumours whereas other studies do not. It is concluded that one should be careful using incidence data to dismiss results in analytical epidemiology. The IARC carcinogenic classification does not seem to have had any significant impact on governments' perceptions of their responsibilities to protect public health from this widespread source of radiation.
  Pathophysiology 12/2012;
• Article: Anemia associated with extraerythrocytic oxidative stress damage mediated by neutrophil superoxide anion production in chronic renal failure patients undergoing hemodialysis.

  Jair Tonon, Flávia Alessandra Guarnier, Alessandra Lourenço Cecchini, Rubens Cecchini
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  ABSTRACT: Anemia in patients with uremia undergoing hemodialysis (HD) is a complex process that is dependent on erythropoiesis associated with erythropoietin and iron availability. Published information about an extra erythrocytic factor in the data concerning HD and the underlying mechanism by which anemia occurs remain unclear. The aim of this study was to investigate the superoxide anion generation by polymorphonuclear neutrophils and red blood cell (RBC) lipid peroxidizability as well as the possible association between these parameters and anemia in patients undergoing HD. Blood was collected from 15 volunteers prior to and following HD, and hematological data showed significant anemia at both time points. RBC lipid peroxidizability and neutrophil anion superoxide production, as evaluated by kinetics analysis, revealed increased initial and maximal velocity before and after HD. Plasma malondialdehyde (MDA) and antioxidant levels in the patient group were higher than those in the control group. RBC superoxide dismutase and catalase activities did not differ between groups. There was a significant correlation between increased RBC lipid peroxidizability and superoxide anion production and anemia in patients undergoing HD. The individual variation in plasma MDA was accompanied by superoxide anion production. The RBC lipid peroxidizability, mediated by neutrophil-generated superoxide anions, seems to be a plausible mechanism for explaining, in part, the extraerythrocytic damage that leads to anemia in patients on HD.
  Pathophysiology 10/2012;
• Article: Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size.

  Enildo Broetto Pimentel, Andrea Cruz de Moraes, Ludimila Forechi, Rebeca Caldeira Machado, Marcelo Perim Baldo, Jose Geraldo Mill
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  ABSTRACT: The electrocardiogram (ECG) has been a useful tool to identify ischemia in humans and laboratory animals. Previous ECG studies showed that presence of pathological Q waves in lead DI in rats submitted to ligature of the left coronary artery (LCA) is a good predictor of successful myocardial infarction (MI). This study aimed to determine the sensitivity and the specificity of these ECG findings to predict successful MI. Male Wistar rats were submitted to surgical ligature of the LCA (N=86) or sham-operation (SO, N=16). ECG was recorded under halothane/ether anesthesia before surgery and 1, 3, 5, 7, and 15 days later. MI was determined by the presence of a transmural fibrous scar. Sixty-nine rats survived and 60 showed fibrous scar indicating a successful production of MI (18 and 42 animals were analyzed 1 or 15 days after MI, respectively). Twenty-four hours after, Q amplitude was linearly related to infarct size (r=-0.778; P<0.01), but not 15 days after (r=-0.416; P>0.05). In 53 out of 60 rats with transmural scar, Q wave in lead DI was identified in the ECG. Absence of Q wave occurred in 7 animals. The sensitivity was 88% (CI(95)=83-93%). Nine animals submitted to coronary ligature did not show infarct scar. One of these animals, however, showed Q wave in DI, indicating a specificity of 77% (CI(95)=65-104%). In conclusion, ECG can be used as a reliable tool to identify MI and can be used to predict the infarct size as earlier as 1 day after LCA ligation in rats.
  Pathophysiology 10/2012;
• Article: Synaptic degradation of cardiac autonomic nerves in streptozotocin-induced diabetic rats.

  Shamarendra N Sanyal, Tomoyuki Wada, Motoko Yamabe, Hirofumi Anai, Shinji Miyamoto, Tatsuo Shimada, Katsushige Ono
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  ABSTRACT: Background: Cardiac autonomic neuropathy (CAN) is a common complication in type I diabetes mellitus (DM). Nevertheless, the relationship between functional and structural disturbances of cardiac autonomic nerves remains unclear. Methods and results: To clarify this relationship, we studied heart rate variability (HRV) and ultrastructural changes of cardiac autonomic nerves in streptozotocin (STZ)-induced DM in rats. STZ was injected (65mg/kg intravenous) into the tail vein of male Wistar rats to destroy β cells in the pancreatic islets. After STZ injection, fasting blood sugar (FBS) increased from baseline values of 75±3mg/dl up to 328±12mg/dl within 1week and it reached up to 353±24mg/dl within 17weeks. HR in these rats was decreased within 20days and low HR was maintained for the observation period. TP and HF power started decreasing 20days after STZ injection, and this decrease progressed throughout the observation period. The L/H power ratio was decreased 80days after STZ. Electron microscopic findings indicated a depletion of neurotransmitter vesicles and degradation of parasympathetic nerve endings but not of sympathetic ones in the SA node region of the heart in the early stages of DM. In the late stages of DM, the same region showed degradation of both sympathetic and parasympathetic nerve endings. Conclusion: Synaptic degradation in parasympathetic nerves immediately after the onset of DM, and in sympathetic nerves much later in the development of DM is consistent with functional derangements in cardiac autonomic nerve activities assessed by HRV analysis.
  Pathophysiology 09/2012;
• Article: Interplanetary space flight compared with fetal/neonatal motor strategy: Theoretical and practical implications.

  Alexander Meigal
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  ABSTRACT: The condition of simulated or real manned spaceflight, i.e. thermally comfortable microgravitation (G∼0), is very similar to the intrauterine immersion to the amniotic fluid. Domination of fast muscle fibers and phasic movements forms the fetal strategy to survive in heating, strongly hypoxic, albeit normal for fetus, immersion. In adults, the adaptive response separately to microgravitation, heat stress and hypoxia also shifts muscle fiber properties to faster values. That allows to speculate about specific motor strategy induced by micro-or hypogravitation (fetal/microgravitation, or FM-strategy). After birth the newborn is subjected to a combined 'sensory attack' of Earth gravitation, cooler ambient temperature and normoxia which is actually hyperoxic for fetus. The process of parturition can be considered as equivalent to cosmonaut's/astronaut's transition from microgravitation back to Earth gravitation (G=1) during landing. These factors also act simultaneously and constitute another set of sensory inputs with the effect that is opposite to the intrauterine condition. In normal gravitation, comfortable temperature and normoxia decreases the motor unit activity (MU) firing rate to a level, characteristic for the regular Earth condition. In contrast to 'faster' fetal adaptive motor response (microgravitation, heat, hypoxia), the post-natal adult set of conditions (lower, but still normal temperature, normoxia, 1G gravitation, healthy maturation) may represent the 'Earth' adaptive motor response, or the (gravitation/Earth, or GE-strategy). The motor system undergoes a second profound remodeling in older people during healthy ageing that results in further domination of slow muscle fibers and slowing down motor unit activity, simulating the condition of hypergravitation (G>1). Similar slowing adaptive responses are represented by cold and hyperoxia thus forming further motor strategy that could be named as SJ-strategy (after 'slow' and Jupiter - the most massive planet and the only planet with G>1 in the solar system). These strategies suppose that definite sensory inputs and conditions may substitute each other due to its equivalent action on the motor system. Thus, cold 'sensory attack' may serve as a 'surrogate' for gravitation because these two conditions exert equivalent stimulating action on muscle tone. In that respect long-term mild cooling exposures or shorter severe cold exposures may be considered as a prophylactic countermeasure against hazardous action of weightlessness. Also, combination of cooling sensory intervention with traditional and well- documented interventions (whole body vibration and stimulation of 'support zone' afferents) may elevate their anti-microgravitation efficiency.
  Pathophysiology 09/2012;
• Article: On the association between glioma, wireless phones, heredity and ionising radiation.

  Michael Carlberg, Lennart Hardell
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  ABSTRACT: We performed two case-control studies on brain tumours diagnosed during 1 January 1997 to 30 June 2000 and 1 July 2000 to 31 December 2003, respectively. Living cases and controls aged 20-80 years were included. An additional study was performed on deceased cases with a malignant brain tumour using deceased controls. Pooled results for glioma yielded for ipsilateral use of mobile phone odds ratio (OR)=2.9, 95% confidence interval (CI)=1.8-4.7 in the >10 years latency group. The corresponding result for cordless phone was OR=3.8, 95% CI=1.8-8.1. OR increased statistically significant for cumulative use of wireless phones per 100h and per year of latency. For high-grade glioma ipsilateral use of mobile phone gave OR=3.9, 95% CI=2.3-6.6 and cordless phone OR=5.5, 95% CI=2.3-13 in the >10 years latency group. Heredity for brain tumour gave OR=3.4, 95% CI=2.1-5.5 for glioma. There was no interaction with use of wireless phones. X-ray investigation of the head gave overall OR=1.3, 95% CI=1.1-1.7 for glioma without interaction with use of wireless phones or heredity. In conclusion use of mobile and cordless phone increased the risk for glioma with highest OR for ipsilateral use, latency >10 years and third tertile of cumulative use in hours. In total, the risk was highest in the age group <20 years for first use of a wireless phone.
  Pathophysiology 08/2012;
• Article: Cardiac autonomic nerve abnormalities in chronic heart failure are associated with presynaptic vagal nerve degeneration.

  Shamarendra N Sanyal, Tomoyuki Wada, Motoko Yamabe, Hirofumi Anai, Shinji Miyamoto, Tatsuo Shimada, Katsushige Ono
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  ABSTRACT: Background: Understanding of the functional and structural disturbances of cardiac autonomic nerves in ventricular hypertrophy and eventual chronic heart failure (CHF) remains unclear. Methods and results: ECG signals were obtained by a radio transmitter from male Wistar rats that received monocrotaline (MCT) via subcutaneous injection. Heart rate (HR) and HR variability (HRV) were analyzed. The RR interval, total power (TP), low frequency (LF) power, high frequency (HF) power, and LF/HF (L/H) power ratio were measured. Ultrastructural changes in cardiac autonomic nerves at the sinoatrial (SA) node region were studied using an electron microscope. TP and HF powers in MCT-induced right ventricular hypertrophy (RVH) and eventual CHF were significantly decreased, and HR was significantly increased at week 5 or later after the MCT injection. The electron microscopic findings indicated the depletion of neurotransmitter vesicles and degradation of parasympathetic but not sympathetic nerve endings in the SA node region of the heart. Conclusion: MCT-induced RVH and CHF rats showed presynaptic vagal nerve degradation prior to sympathetic nerve derangement in the heart.
  Pathophysiology 08/2012;
• Article: Blood pressure surges in REM sleep: A mini review.

  Hiroyoshi Séi
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  ABSTRACT: Blood pressure displays large fluctuations during REM sleep, a period when skeletal muscle loses activity systemically. Blood pressure rises spontaneously in spike-like surges even with no body movement. The mechanism underlying this unique characteristic of cardiovascular control during REM sleep remains unclear. Where does the source for this blood pressure surge during REM sleep exist? Is it related to dreaming, which is one of the primary characteristics of REM sleep? Are peripheral mechanisms involved in this phenomenon? Here, evidence related to the above-mentioned questions is reviewed.
  Pathophysiology 08/2012;
• Article: Pathophysiological function of oxytocin secreted by neuropeptides: A mini review.

  Hirofumi Hashimoto, Yasuhito Uezono, Yoichi Ueta
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  ABSTRACT: Oxytocin (OXT) is well known for its ability to stimulate milk ejection and uterine contraction. OXT is also involved in several physiological and pathological functions such as antinociception, anxiety, feeding, social recognition and stress responses. Previous studies showed that neuropeptides such as cholecystokinin (CCK) activate OXT-secreting magnocellular neuron in the supraoptic (SON) and the paraventricular nuclei (PVN) of the hypothalamus and cause OXT release from the axon terminal in the posterior pituitary into the systemic circulation. Our recent studies showed that central administration of adrenomedullin (AM) family (AM, AM2 (identical to intermedin) and AM5) induced the expression of the c-fos gene in the SON and the PVN and elicited the marked increase of plasma OXT levels in conscious rats. Here, we review pathophysiological properties of OXT in whole body and effects of novel peptides such as AM family as well as other peptides on OXT release.
  Pathophysiology 08/2012;
• Article: HIF-3α mRNA expression changes in different tissues and their role in adaptation to intermittent hypoxia and physical exercise.

  T Drevytska, B Gavenauskas, S Drozdovska, V Nosar, V Dosenko, I Mankovska
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  ABSTRACT: The role of HIF-3α in response to intermittent hypoxia and physical exercise was investigated in Fisher rats using reverse transcription, real-time PCR and RNA interference. Under acute hypoxia (12% O(2), 2h), the level of HIF-1α, HIF-2α, and HIF-1β mRNA did not significantly change in the heart, lung, kidney and muscle tissues, but HIF-3α mRNA expression was strongly elevated in all tissues investigated. Five weeks of intermittent hypoxic training (IHT) led to an increase of HIF-3α mRNA in all studied tissues, but under the influence of acute hypoxia after IHT, the expression of HIF-3α mRNA did not increase in all tissues excluding skeletal muscle. Thus, IHT reduced the effect of acute hypoxia on HIF-3α mRNA expression in the heart, lung, and kidney. The expression of HIF-3α in skeletal muscle at endurance (swimming) training (ET) in combination with IHT was 6.2 times lower compared to the group with ET but without IHT and 3.3 times lower (P<0.05) compared to untrained control. After swimming training with IHT, rats demonstrated the highest level of physical endurance. RNA interference of HIF-3α significantly decreased the level of HIF-3α mRNA in both muscles investigated: by 2.6 times in m. soleus (P<0.03) and by 2.1 times in m. gastrocnemius (P<0.05) and elevated the physical endurance of rats by 50% (P<0.05) compared to control. Thus, the HIF-3α subunit is an essential member of hypoxic response. It plays a negative role in the adaptation to hypoxia, because the inhibition of HIF-3α expression leads to an increase in physical endurance.
  Pathophysiology 08/2012; 19(3):205-14.
• Article: The impact of psychogenic stressors on oxidative stress markers and patterns of CYP2E1 expression in mice liver.

  Oksana Maksymchuk, Mykola Chashchyn
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  ABSTRACT: The increasing number of psychogenic stressors is a side effect of civilization. It results in the development of psychoemotional stresses and psychosomatic diseases. In this study we evaluated the effect of the chronic psychoemotional stress on the level of CYP2E1 expression in the liver of C57Bl/6 mice. Stress was induced by the immobilization of animals for 4h per day during 7 or 14 days. CYP2E1 expression level was evaluated on the 7th and 14th days of the experiment, respectively. We detected a twofold reduction in CYP2E1 protein expression level relatively to controls for both time points tested. This reduction was no longer significant when the effect of the stressor factor was terminated on the 14th day of the experiment and animals were analyzed one week later. Remarkably Cyp2e1 mRNA expression level was constant at any time point of the experiment. We also documented significant changes in the expression/activity of two oxidative stress markers examined in the liver of treated mice. The catalase activity decreased fivefold while malondialdehyde transiently increased threefold. These data suggest that oxidative stress can be involved in the reduction of hepatic CYP2E1 and catalase activity under the conditions of chronic emotional stress.
  Pathophysiology 08/2012; 19(3):215-9.
• Article: Global electromagnetic toxicity and frequency-induced diseases: Theory and short overview.

  Sergio Manzetti, Olle Johansson
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  ABSTRACT: The development and implementation of electricity in the modern society have facilitated the survival of mankind in the present, modern ages. However, the health consequences of introducing electricity into the society are poorly studied. Studies of artificial light and non-ionizing radiation are generally low priorities on the agenda of public health organizations, and the reported existing data indicate that there are several unanswered questions to whether humans are negatively affected in electrified environments. This article discusses the potential aspects of the impact of electricity on human health and brain function and introduces a hypothesis. The article furthermore discusses the disturbance of sleep patterns caused by electrified environments, and the increasing absence of natural stimuli to the human brain causing chronic 'digital stress' facilitating pathophysiological development. A significant need to study adverse health effects from non-ionizing radiation and synthetic luminous environments from an environmental toxicological perspective is definitely urged.
  Pathophysiology 07/2012; 19(3):185-91.