Pathophysiology

Editorial Board

2012-02-01

WHO recognizes electromagnetic dangers: let us declare human health rights

Cindy Sage, Paavo Huttunen — 2012-02-01

On May 31, 2011 the International Agency for Research on Cancer (IARC) classified radiofrequency radiation (RFR) as a 2B Possible Human Carcinogen, in the same category as exhaust, DDT and lead. This represents a global shift in scientific and public health thinking.

Bone marrow stem cells repopulate thyroid in X-ray regeneration in mice

2012-02-01

Highlights: ► Bone marrow stem cells contribute into thyroid regeneration after X-ray exposure. ► Chronic experiment reveals both follicular and intrafollicular thyrocytes involved. ► Parabiosis method provides data correlated to BMSC injection method in miceAbstract: The aim of this study was to clarify the regeneration mechanisms of thyroid in post-irradiated C57Bl/6 mice chimeric with transgenic green fluorescent protein (GFP) positive C57Bl/6 mice after 5 and 7.5Gy X-ray exposures with the aid of morphological and immunocytochemical research of GFP-positive cell distribution. Cryostat slides of larynxes with thyroid glands were fixed by mixture of cold methanol and ethanol, cell nuclei were stained with propidium iodide. After immunocytochemical staining the slides of larynx with thyroid gland were investigated by means of confocal LSM 5 PASCAL microscope. True GFP nature of green signals in tissue slides was confirmed via additional treatment by anti-GFP antibody and Texas Red labeled second antibody. Separate GFP-positive cells were observed in the walls of follicles and between follicles of chimeric mice 9–10 months after X-ray exposure. GFP signal was viewed as cytoplasmic droplets and within the colloid of follicles. The share of GFP-positive follicles reached 6.1±1.8%. There was also co-localization of GFP signals and positive staining for thyroglobulin by monoclonal antibody. As many as 20.8±1.8% among all propidium iodide positive blood cells and 52.3±8.3% among propidium iodide positive bone marrow cells were at the same time GFP-positive. In conclusion, the results show that the bone marrow stem cells participate in the thyroid gland regeneration after 5Gy X-ray exposure.

Contribution of nitric oxide synthase (NOS) in blood–brain barrier disruption during acute focal cerebral ischemia in normal rat

Mohammad T. Mohammadi, S. Mostafa Shid-Moosavi, Gholam A. Dehghani — 2012-02-01

Abstract: Endogenous level of nitric oxide (NO) is increased in the brain following the stroke, and deactivation of NO synthase has been shown to attenuate its destructive actions in animal stroke models using middle cerebral artery occlusion (MCAO) procedures. However, little is known about the effects of NO in cerebral vascular integrity and edema during acute cerebral ischemia. Here we investigated whether NO plays any role in the progression of blood–brain barrier (BBB) disruption and edema formation in ischemia/reperfusion injury. Intraperitoneal administration of NO substrate l-arginine (300mg/kg), or NOS inhibitor (l-NAME, 1mg/kg), was done in normal rats at 20min before a 60-min MCAO. Mean arterial blood pressures (MAP) and regional cerebral blood flow (rCBF) were continuously recorded during experiment. Neurological deficit score (NDS) was evaluated 12h after termination of MCAO followed with evaluations of cerebral infarction volume (CIV), edema formation and cerebral vascular permeability (CVP), as determined by the Evans blue dye extravasations (EBE) technique. No significant changes were observed in the values of MAP and rCBF with l-arginine or l-NAME during ischemia or reperfusion periods. There was a 75–85% reduction in rCBF in during MCAO which returned back to its pre-occlusion level during reperfusion. Acute cerebral ischemia with or without l-arginine augmented NDS (4.00±0.44 and 3.00±0.30), in conjunction with increased CIV (518±57mm3 and 461±65mm3), provoked edema (3.09±0.45% and 3.30±0.49%), and elevated EBE (8.28±2.04μg/g and 5.09±1.41μg/g). Inhibition of NO production by l-NAME significantly improved NDS (1.50±0.22), diminished CIV (248±56mm3), edema (1.18±0.58%) and EBE (1.37±0.12μg/g). This study reconfirms the cerebroprotective properties of reduced tissue NO during acute ischemic stroke, and it also validates the deleterious actions of increased NOS activity on the disruption of cerebral microvascular integrity and edema formation of ischemia/reperfusion injuries in normal rat, without changing arterial blood pressure or blood flows to ischemic regions.

Cancer risks in the Druze Isifya Village: Reasons and RF/MW antennas

Iris Atzmon, Shai Linn, Elihu Richter, Boris A. Portnov — 2012-02-01

Highlights: ► We examined the claims of the residents of the Druze Isifya Village in Northern Israel that their high cancer rates were associated with the past exposures to radiation from radio and cellular transmitters. ► We carried out a population-based case-control study involving 307 residents, of whom 47 were diagnosed between 1989 and 2007 with different types of cancer and 260 controls. ► We found evidence for an increased risk of cancers associated with chemicals in manufacturing and agriculture and electronics, but not with exposures to EMF.Abstract: Background: The present study was initiated to examine the claims of the residents of the Druze Isifya Village in Northern Israel that their high cancer rates were associated with the past exposures to radiation from radio and cellular transmitters. Objective: To investigate the association between past exposure to RF/MW transmitters and cancer risks, taking into account familial cancer history, occupational exposures and indicators of life-style. Methods: We carried out a population-based case-control study involving 307 residents, of whom 47 were diagnosed between 1989 and 2007 with different types of cancer and 260 controls. Cancer diagnoses were obtained from medical the records. Exposure status of individual houses were determined from a map, based on the distances between each house and RF/MW antennas, and were calculated using geographic information systems (GIS) tools. Data on additional risk factors for cancer, like smoking and occupation, were obtained from individual questionnaires. The analysis was adjusted for measures of life style and occupational exposure, and Binary multiple logistic regressions was used, for all cancer sites and for individual cancer types for those cancers with at least 5 documented cases. Results: Past occupational exposures to chemicals (e.g., pesticides) and electronics, were found to be strongly associated with increased cancer risks (all sites: OR=2.79; CI=1.14–6.82; P<0.05), but no discernible trend in overall cancer risk was associated with proximity to sources of past RF/MW radiation exposure (n=47 OR=1.00; CI=0.99–1.02; P>0.4). Colorectal cancer showed a negligible elevated adjusted risk associated with radiation intensity (n=11 OR=1.03; CI=1.01–1.05; P<0.01). Conclusion: There was evidence for an increased risk of cancers which were associated with chemicals in manufacturing and agriculture and electronics, where there may have been exposures to EMF, but the study did not confirm the suspicion of increased cancer risks associated with radiation for most cancer types in this village. Misclassification of past exposures could explain the negative finding.

Combined estrogen–progestogen but not progestogen-only oral contraceptive alters glucose tolerance and plasma lipid profile in female rats

L.A. Olatunji, O.S. Michael, F.O. Adewumi, I.J. Aiyegboyin, V.A. Olatunji — 2012-02-01

Abstract: Women are exposed to sex steroids in several formulations such as oral contraceptives (OCs) and hormone replacement therapies. Estrogen is believed to have cardiometabolic protection effect; but its beneficial effects have recently been queried. The aim of the present study was to clarify whether or not the altered glucose tolerance and plasma lipid profile was associated with OC and due to the estrogenic or progestogenic-component and if that was dose-dependent in 7–8 weeks old female rats. Rats were divided into vehicle-treated (control), high dose combined OC-treated (HCOC; receiving 1.5μg ethinyl estradiol/15.0μg norgestrel), low dose combined OC-treated (LCOC; receiving 0.15μg ethinyl estradiol/1.5μg norgestrel), high dose progestogen OC-treated (HOC; receiving 35.0μg levonorgestrel) and low dose progestogen OC-treated (LOC; receiving 3.5μg levonorgestrel) groups. Rats were given (p.o.) vehicle (distilled water), HCOC, LCOC, HOC and LOC daily for 6 weeks. When compared with the controls, HCOC treatment led to significant decreases in glucose tolerance and plasma high-density lipoprotein-cholesterol. However, HCOC-treated and LCOC-treated groups had significantly higher plasma triglyceride levels when compared with the control group. Fasting blood glucose, plasma total cholesterol, and low-density lipoprotein-cholesterol were comparable among groups. Body weight gain appeared to be attenuated by OC treatments, particularly in LOC-treated rats. In conclusion, our findings demonstrate that combined estrogen–progestogen but not progestogen-only OC use resulted in impaired glucose tolerance that was associated with increased triglyceride and decreased high-density lipoprotein-cholesterol. The effects on glucose tolerance and high-density lipoprotein-cholesterol were dose-dependent while that on triglyceride was not.

Antihyperglycemic, antihyperlipidemic and antioxidant activities of traditional aqueous extract of Zygophyllum album in streptozotocin diabetic mice

Jamel El Ghoul, Moêz Smiri, Saad Ghrab, Naceur A. Boughattas, Mossadok Ben-Attia — 2012-02-01

Abstract: Objective: The aim of this work was to investigate the antihyperglycemic, antioxidant and antihyperlipidemic effects of the aqueous extract of Zygophyllum album on streptozotocin (STZ)-induced diabetic mice. Methods: Diabetes was induced in Swiss albino mice by the administration of STZ (45mg/kg b.w.) intraperitoneally. Aqueous extract of Z. album (100 and 300mg/kg b.w.) was administered by oral gavage once a day for a period of 15days. The effect of the extract on blood glucose, lipids, cholesterol levels in plasma, and also on enzymatic and non enzymatic antioxidants of defence systems such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme activities, and vitamin C, vitamin E and glutathione reductase (GSH) levels in liver and pancreas were studied. Results: Our results showed that Z. album extract reduced the blood glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) levels in STZ-diabetic mice. It also significantly abolished the increase in MDA level, and GPx, SOD and CAT activities in both liver and pancreas. The levels of GSH, vitamin C and high-density lipoprotein (HDL) were significantly augmented in Z. album treated diabetic mice in comparison with control group. Our findings suggest that Z. album aqueous extract prevented the diabetic induced MDA levels via the enhancement of the tissue GSH and blood vitamin C levels. Conclusions: These results suggest that Z. album extract exerts the anti-diabetic and antihypercholesterolemic activities through its antioxidant properties.

Mobile phone radiation interferes laboratory immunoenzymometric assays: Example chorionic gonadotropin assays

2012-02-01

Highlights: ► Human Chorionic Gonadotropin was exposed to microwaves emitted from cell phones. ► Cell phones exposure causes profound changes in the HCG during immunoenzymometric assay. ► The exposure results in reduction of HCG scores during the assay. ► Exposure at 0.69W/Kg gives little loose to a pronounced HCG relative to 1.09W/Kg. ► These results were obtained by using mobile phones to reproduce the reality of the human exposition.Abstract: The radiofrequency radiation is of concern in hospital laboratories as the microwaves have many health effects even on immune functions. The aim of this study was, however, to evaluate the effects of cell phone radiation on chorionic gonadotropin immunoassays of human serum. Two cell phones with 0.69 and 1.09W/kg (head SAR) emitting 900MHz radiation were used. Sixty wells with five human serum concentrations (0, 10, 100, 250, 500mIU/mL) were used in three batches. The well heads in each batch were exposed to 900MHz emitted from these phones, and the 0.69, 1.09W/kg exposed batches were compared with the unexposed controls. Radiation exposure from mobile phones altered the measured serum levels especially in the wells with 100, 250, 500mIU/mL hormone concentrations. Exposure at 1.09W/kg SAR caused a significant loss compared to 0.69W/kg SAR exposure. In conclusion, the microwave exposures may require attention in laboratories using immunoassays.

Effect of binge ethanol treatment on prooxidant–antioxidant balance in rat heart tissue

2012-02-01

Highlights: ► Effects of binge ethanol drinking on cardiac function are examined in female rats. ► Serum cardiac enzyme activities are elevated. ► Heart lipid peroxidation parameters are increased. ► Antioxidant system is unaffected other than increased superoxide dismutase activity.Abstract: Binge drinking of alcohol is known to cause cardiac dysfunction in some drinkers. This study was designed to examine the effect of ethanol on rat heart tissue with an experimental model mimicking human binge drinking. Female Sprague-Dawley rats were given ethanol diluted with normal saline (40%, v:v) by gavage at the dose of 5.0g/kg every 12h for 3 doses as total. Serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK) and aspartate transaminase (AST) were determined. Endogenous lipid peroxidation was assessed by measuring the levels of malondialdehyde (MDA) in heart homogenates. In vitro susceptibility of tissues to oxidative stress was assessed by using two different media. Tissue glutathione (GSH) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. All serum enzymatic activities were found markedly elevated in ethanol group. Binge ethanol administration significantly enhanced endogenous lipid peroxidation and caused an enhanced in vitro susceptibility to lipid peroxidation. Levels of reduced GSH and GSH-Px and GST activities were found unchanged as compared to controls. SOD activity was found significantly increased. As a conclusion, binge ethanol consumption which was applied to rats to investigate acute tissue injury, appeared to confirm the generation of oxidative stress in rat hearts.

Mechanism of non-specific-fistula-in-ano: Hormonal aspects—Review

A.M. El-Tawil — 2012-02-01

Abstract: Abscesses could occur anywhere, but quite few that could proceed forward and develop fistulae. Crypto glandular abscess formation concept has been forming the basis for almost all designed strategies for management of cases of idiopathic fistula-in-ano for ages. Yet, this hypothesis failed to explain the reason(s) for the recorded lower incidences of idiopathic anal fistula in females than in males.Gram negative bacteria are largely the causative agents for these anal glands’ abscesses that processed further and developed fistulae. Lipopolysaccharide component (LPS) of the bacterial cell wall could significantly attenuate the expression of mRNA of the oestrogen receptors and accordingly reduces the down signalling pathway. Yet, this kind of action could be inhibited in the presence of oestrogen.In addition, tumour necrosis factor-alpha (TNFα) is a key proinflammatory cytokine that induces the secretion of other cytokines and enzymes in various cells and tissues. And LPS could activate pro-inflammatory cytokine by activating plasma membrane proteins (e.g. the toll like receptor 4 [TLR4] and CD14 that leads to the production of TNFα and other pro-inflammatory cytokines). This activation could be enhanced by testosterone but inhibited by oestrogen. These are likely the reasons for the higher prevalence of idiopathic fistula-in-ano in males than in females.

Letter to the Editor

R. Glaser, Ch. Bornkessel — 2012-02-01

Adamantia Fragopoulou et al. reported on “Cranial and postcranial skeletal variations induced in mouse embryo by mobile phone radiation” (Pathophysiology 2009, received 25 August 2009), and found “variations in the exposed foetuses with respect to control ones concerning the ossification of cranial bones and thoracic cage ribs, as well as displacement of Meckelian cartilage”. This could be an important finding, in contrast to negative results of others (non mentioned in the paper: Sommer et al. and Ono et al. ) but unfortunately, there are various experimental problems and obscurities in the text which induce some ambiguities and doubts.

Reply to Drs. R. Glaser and Ch. Bornkessel

L.H. Margaritis, S.L. Koussoulakos, A.F. Fragopoulou — 2012-02-01

Sommer et al. studied “the fertility and development of the animals”, but we did not study fertility. We also performed studies in different frequency and exposure conditions. Also Ono et al. studied mutagenesis and aging in a different frequency EMF (2.45GHz) and produced by a generator and not by mobile phone.

Are polycyclic aromatic hydrocarbons from fossil emissions potential hormone-analogue sources for modern man?

Sergio Manzetti — 2012-02-01

Polycyclic aromatic hydrocarbons are a group of carcinogenic and mutagenic molecules and ubiquitous environmental pollutants that are generated from natural and anthropogenic sources such as fossil fuel emissions, cigarette smoke, industrial combustion and incineration plants and are a continuous health threat to the human population .

Corrigendum to ‘Testosterone relaxes abdominal aorta in male Sprague–Dawley rats by opening potassium (K+) channel and blockade of calcium (Ca2+) channel’ [Pathophysiology 18 (3) (2011) 247–253]

2012-02-01

The authors regret the omission of a co-author's name: Anigbogu Chikodi N. Department of Physiology, College of Medicine, University of Lagos. The authors would like to apologise for any inconvenience caused.