Dexmedetomidine and propofol sedation requirements in an autistic rat model / 대한마취과학회지

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.

Dexmedetomidine and propofol sedation requirements in an autistic rat model / 대한마취과학회지

BACKGROUND@#Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms.@*METHODS@#Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed.@*RESULTS@#Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats.@*CONCLUSIONS@#This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.

Amelioration of insulin resistance in rats treated with rice bran oil

Background: insulin resistance [IR] is a pathological condition characterized by inadequate peripheral tissue metabolic response to circulating insulin. It plays pathophysiological role in type 2 diabetes mellitus [T2DM]. High dosage of fructose in the diet [60 g/100 g diet] may induce insulin resistance accompanied by deleterious metabolic consequences including hyperglycemia and hyperinsulinemia. Rice bran oil [RBO], is a rich source of antioxidants especially gamma-oryzanol, alpha-tocopherols and tocotrienols which contribute to high oxidative stability, longer shelf life than other edible oils and high antioxidant property against free radicals. The present work was undertaken to study if the addition of rice bran oil in rat's diets ameliorate the insulin resistance

Materials and methods: to achieve this target, plasma fasting glucose, serum insulin and calculated HOMA-IR, which assesse the presence of insulin resistance, was evaluated. Serum lipid profile [cholesterol, triglycerides, high-density lipoprotein- cholesterol [HDL] and low-density lipoprotein- cholesterol [LDL] was also evaluated. In addition, the oxidative stress was assessed through hepatic malondialdehyd [MDA] as an oxidative biomarker and the antioxidant enzyme superoxide dismutase [SOD] was also estimated

Results: RBO ameliorated HOMA-IR, oxidative biomarker [MDA] and increased SOD activity

Conclusion: high fructose diet induced oxidative stress which lead to insulin resistance, this was ameliorated by addition of RBO

Thiobarbituric acid reactive substance [TEARS] a marker of oxidative stress in obstructive sleep apnea

OSA is a common condition that is primarily characterized by intermittent and recurrent pauses in respiration results in multiple cycles of hypoxia/re-oxygenation with an increased production of reactive oxygen species [ROS]. Is to assess TEARS as a marker of oxidative stress in obese patients with and without OSA. Study was performed on 51 obese subjects who had been referred to the Chest Department of Kasr Alaini Hospital with clinical suspicion of OSA in order to perform pol-ysomnography. They were classified into two groups; Cases: consist of 33 obese patients who were diagnosed as obstructive sleep apnea [OSA] and Controls: consist of 18 obese subjects, without OSA as a control group. The two groups were subjected to polysomnograpic study and serum TEARS. There was statistically highly significant increase in Epworth sleepiness scale [ESS] among cases compared to controls. As regards the polysomnographic data, there was statistically highly significant increase in AHI, desaturation index and duration of desaturation < 90% among cases compared to control subjects. While minimal O[2] sat% and average O[2] sat% were lower in cases than in the control subjects this reduction was statistically significant. There was statistically highly significant increase in serum TEARS levels among cases as compared to controls. There was a statistically significant positive correlation between grade of obesity and serum TEARS among studied cases. TERAS could be used as a marker of oxidative stress in OSA

Insulin resistance in obstructive sleep apnea

OSA is a common condition that is characterized by intermittent and recurrent pauses in respiration results in multiple cycles of hypoxia/reoxygenation with an increased production of reactive oxygen species [ROS]. Is to assess serum insulin level and insulin resistance in obese patients with and without OSA. Study was performed on 51 obese subjects who had been referred to the Chest Department of Kasr Alaini Hospital with clinical suspicion of OSA in order to perform polysomnography. They were classified into two groups; cases: consist of 33 obese patients who were diagnosed as obstructive sleep apnea [OSA] and controls: consist of 18 obese subjects, without OSA as a control group. The two groups were subjected to polysomnographic study, serum insulin by ELISA and assessment of insulin resistance by calculation of HOMA index. There was statistically highly significant increase in Epworth sleepiness scale [ESS] among cases compared to controls. As regards the polysomnographic data, there was statistically highly significant increase in AHI, desaturation index and duration of desaturation < 90% among cases compared to control subjects. Regarding minimal O2 sat% and average O[2] sat% were lower in cases than in the control subjects and this reduction was statistically significant. There was statistically highly significant increase in serum insulin, HOMA index among cases as compared to controls. Insulin resistance in OSA is related to sleep associated hypoxemia and hypoxic stress

New Approach of Bone Marrow-Derived Mesenchymal Stem Cells and Human Amniotic Epithelial Cells Applications in Accelerating Wound Healing of Irradiated Albino Rats

BACKGROUND AND OBJECTIVES: Irradiated wound healing is a highly complex and dynamic process. The latest technology making a huge difference in this process is stem cell therapy. The goal of this study was to evaluate the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) or human amniotic epithelial cells (HAECs) in the healing of irradiated wounds. METHODS AND RESULTS: Forty five male albino rats were subjected to whole body 6 gray gamma radiations. One day post irradiation, full-thickness incisional wound was created in the tibial skin. The rats were randomly equally divided into three groups. The incisions of the first group (gp I) were injected intra-dermally with saline before stitching and those of both the second (gp II) and the third groups (gp III) were intradermally injected with BM-MSCs and HAECs before stitching respectively. Animals were sacrificed after the third, seventh and fourteenth days postoperative. The healing process was assessed histopathologically. CXCL-5, SDF-1 and Transforming growth factor-beta 1 (TGF-beta1) expression were also detected in biopsies from all wounds. Expression of TGF-beta1 in gp I was more than the other groups leading to severe inflammation, deficient healed dermis and delayed reepithelialization. SDF-1 expression was high in gp II while CXCL-5 expression was high in gp III causing accelerated wound healing. BM-MSCs showed a great effect on the quality of the dermis, while superiority of the epithelium and its appendages were achieved in HAECs group. CONCLUSIONS: Using BM-MSCs and HAECs could be used safely in case of irradiated wounds.

Association of tumor necrosis factor-alpha polymorphisms with susceptibility and clinical outcomes of rheumatic heart disease

To examine the association of tumor necrosis factor-alpha [TNF-alpha] gene polymorphisms with rheumatic heart disease [RHD] and valve damage, and their influence on TNF-alpha production and disease outcome. We performed this cross-sectional study at Kasr El-Aini Hospital, Cairo University, Cairo, Egypt, from December 2008 to October 2009. Eighty children with chronic RHD and valve affection, and 50 controls were included. Patients with any other diseases or complications were excluded. Blood samples [5 ml] were collected. Genotyping for TNF-alpha polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Serum TNF-alpha was measured by enzyme-linked immunosorbent assay. Serum TNF-alpha was significantly increased in RHD compared with controls [p=0.00003]. The TNF-alpha-238 adenine [AA] [p=0.036] and-308AA [p=0.003] genotypes were more frequent in RHD patients than in controls, and were associated with increased production of TNF-alpha [p=0.00001 for 238AA] and [p=0.001 for 308AA]. Both polymorphisms contributed to increased susceptibility for RHD [-308AA and adenine guanine [AG], odds ratio [OR]=4.72 [95% confidence interval [CI] 2.03-11.05], p=0.0001]; [-238 AA and AG, OR=2.33 [CI: 1.05-5.19], p=0.035]. The presence of-308AA was associated with mitral [p=0.001] and multivalvular [p=0.003] lesions and was more prevalent in moderate [p=0.001], and severe [p<0.001] cases than in controls. The-238AA variant was associated with mitral lesions [p=0.04] and severe cases [p=0.05] as compared with controls. The TNF-alpha-238G/A and-308G/A polymorphisms were associated with susceptibility to RHD and increased production of TNF-alpha. Both polymorphisms were related to valve damage, and a more severe outcome of RHD

Adiponectin gene single nucleotide polymorphism 276 G>T associates with low levels of adiponectin in coronary artery disease

Adiponectin is an adipose tissue-specific protein that influences atherosclerosis by its anti-inflammatory properties though modulating cellular processes involved in foam cell formation and by affecting the balance of atherogenic and antiatherogenic lipoproteins in plasma; thus, the adiponectin gene is a potential candidate for the pathogenesis of coronary artery disease [CAD]. In the present work, we studied the association between a single nucleotide polymorphism [SNP] in the adiponectin gene [+276 G>T] as well as plasma adiponectin levels and CAD in a sample of Egyptian patients. The polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method was used to determine the distribution of genotype frequency of the SNP +276G>T in the adiponectin gene and an ELISA was used to determine plasma adiponectin levels, in the current study, we showed a significant difference between patients with CAD and controls as regard adiponectin +276 genotype distribution as well as plasma adiponectin level. Genotypes G/T and G/G represented 79% of CAD patients versus 35.7% of the controls [p<0.05] and plasma adiponectin level was significantly lower in CAD patients than controls [p<0.001]. A significant association between adiponectin SNP at locus 276 and adiponectin level in patients with CAD was observed, with genotype G/G showing the lowest levels, genotype T/T the highest levels, and genotype G/T intermediate levels [p< 0.01]. The adiponectin SNP as well as low adiponectin in CAD was associated with an atherogenic lipid profile and was not affected by the presence or absence of diabetes. In conclusion, the +276 G>T polymorphism can help to identify patients at increased risk of CAD, so that early preventive measures can be undertaken. Adiponectin can he also used as a screening tool, but further research is needed to assess the beneficial effect of modifying its level and its potential therapeutic role

Detection and differentiation of entamoeba histolytica and entamoeba dispar isolates in clinical samples by PCR

A total of 140 out of 180 outpatients attended MISR University for Science and Technology Hospital complained of abdominal pain, diarrhoea and/or dysentery. Stool examination showed 47 [33.6%] had Entamoeba sp., 36 [25.7%] had cysts and 11 [7.9%] had trophozoites. Of 40 asymptomatic ones, 4 [10%] had cysts. A total of 51 positive stool samples for Entamoeba sp. [40 cysts and 11 trophozoites] were tested by Ne-sted Polymerase Chain Reaction [N-PCR] and Restriction Enzyme Digestion [RED] to clarify true E. histolytica from E. dispar. The results showed that 9/51 [17.6%] had E. dispar, while 31 [60.8%] had E. histolytica and 11 [21.6%] had dual infection with both E. histolytica and E. dispar. All E. histolytica PCR proved cases were from the symptomatic group, 11 had trophozoites and 34 had cysts. Thus, the result showed the potential use of molecular tools in detection of E. histolytica and E. dispar, and is a promising tool for epidemiology, particularly to differentiate pathogenic and non pathogenic Entamoeba sp

Impairment of the insulinotropic effect of gastric inhibitory polypeptide [GIP] in obese and diabetic rats is related to the down-regulation of its pancreatic receptors

The association of obesity with type 2 diabetes has been recognized for years. Insulin resistance induced by obesity increases the chances of developing diabetes mellitus in which insulin release is markedly reduced. In type 2 diabetes, there is a possibility that an important part of the impaired insulin secretion is due to loss of the insulinotropic effect of the gastric inhibitory polypeptide [GIP] hormone. The aim of this study was to detect changes that occur in the pancreatic GIP receptor expression and in GIP secretion in obese and type 2 diabetic rats in response to oral glucose administration and its relation to glucose and insulin plasma levels during oral glucose tolerance test [OGTT]. Three groups of rats [n=10/ group] were included in this study: A control group receiving standard chow for 10 weeks, an obese group, in which obesity was induced by feeding rats standard chow with the addition of 32% of the caloric intake as fat for 10 weeks and a type 2 diabetic group, receiving the standard chow with the addition of fructose as 66% of the caloric intake for 10 weeks. Parameters measured in all groups included: Obesity index, systolic blood pressure, serum triglycerides as well as plasma glucose, insulin and GIP levels at 0, 5, 10, 20, 60, 90 and 120min. of an OGTT and pancreatic islets GIP receptors gene expression [GIP-Rs] using PCR method. At the end of 10 weeks, the obese and diabetic groups both had significantly increased fasting plasma glucose levels and insulin resistance indices [HOMA-IR], in addition to significantly higher blood pressure and serum triglycerides levels compared to the control group, indicating the presence of insulin resistance. In addition, the obese group had a significantly increased obesity index and fasting GIP level compared to the control and diabetic groups. During the first 20min. following oral glucose intake, both the obese and the diabetic rats had a significant increase in the glucose excursion compared to that of the control group, with a more significant increase in the diabetic group compared to the obese group. Both the obese and diabetic groups had a significant decrease of early-insulin secretion compared to control, with a more significant decrease in the diabetic group compared to the obese group. During the first 20min. of the OGTT, there was also a significant increase in the incremental change of GIP from 0 to 20min [GIP delta 0-20] in the obese group [60.1 +/- 6.66pmol/L] compared to that of the control [33.96 +/- 4.69pmol/L] and the diabetic [29.34 +/- 2.62pmol/L] groups, which were not significantly different from each other. However, there was a significant decrease of GIP-Rs expression in both the obese [88.07 +/- 10.36 micro g/ml] and the diabetic [87.51 +/- 4.72 micro g/ml] groups compared to the control group [120.35 +/- 8.06 micro g/ml], indicating that the loss of the GIP insulinotropic effect in obese and diabetic rats during the first 20min. of OGTT was due to a reduction in pancreatic GIP-Rs. During the next 20 to 120min. following oral glucose load, plasma GIP was decreasing in all groups, however, the obese group had a significantly increased plasma glucose level compared to the control group and a significant hyperinsulinemia compared to the other two groups. Such hyperinsulinemia in the presence of a decreasing GIP secretion and reduced GIP-Rs indicates the possibility of up-regulation of another compensatory mechanism to overcome the GIP-Rs defect. Moreover, the diabetic group had a significantly increased plasma glucose level compared to that of the other two groups and its plasma insulin level was significantly lower than that of the control group until the 90min. interval and thereafter it showed a non-significant difference with that of the control group. This study revealed that both obese and diabetic rats had an impaired insulinotropic effect of GIP in response to oral glucose administration during OGTT due to impaired gene expression of its pancreatic receptors and not due to impaired secretion. Also there was an associated compensatory hyperinsulinemia in obese rats during the second hour of the OGTT, which may lead to exhaustion of B-cells on the long run, increasing the incidence of diabetes mellitus. Therefore GIP-Rs could be a potential target to prevent transition of obesity to diabetes and to improve insulin secretion in type 2 diabetes mellitus

changes in expression of platelet derived growth factor [PDGF] and PDGF receptor in rat corpus cavernosum after exposure to in vivo hypoxia and cigarette smoking

Platelet derived growth factor [PDGF] over activity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension [hypoxia] and cigarette smoking is a known stimulus for transcriptional induction of [PDGF] ligand and receptor gene. We studied the expression of [PDGF-A] and [PDGFR-beta] in adult male rat isolated corpus cavernosum under hypoxic and cigarette smoking conditions being associated with induction of fibrosis which may lead to erectile dysfunction. Fifty adult male albino rats were used in this experiment. They were divided into 5 groups. Group I [n=10], served as control group. Group II [n=10] rats exposed to acute hypoxia. Group III [n=10] rats exposed to chronic hypoxia. Group IV [n=10] rats exposed to acute cigarette smoking. Group V [n=10] rats exposed to chronic cigarette smoking. In all groups at the end of each experiment corpora cavernosa of all rats were carefully dissected and freed from surrounding tunica albuginia then frozen in -80°C for subsequent reverse transcriptase polymerase chain reaction [RT-PCR]. In all groups of rats PDGF-A and PDGR-m RNA were measured. There was significant increase in PDGF-A mRNA and PDGF- beta receptor in acute hypoxic group, chronic hypoxic group, and chronic cigarette smoking groups of rats compared to control group. It was found that hypoxia, whether, acute or chronic have similar effect of increasing PDGF-A mRNA and PDGF-beta receptor as well as chronic cigarette smoking group of rats. This may lead to erectile dysfunction

Co-infection with cryptosporidium parvum and cyclospora cayetanensis in ummunocompromised patients

Forty nine stool specimens collected from severe diarrheic patients. Eight were suffering from Hodgkin's lymphoma, and the rest were suffering from acute lymph plastic leukaemia. All were examined microscopically for protozoan parasites mainly, Cryptosporidium parvum and Cyclospora cayetanensis. Of the patients, 34 [69.4%] were positive and 15 [30.6%] were negative by both microscopy and nested PCR. An additional 12 [24.5%] who were negative by microscopy were positive by nested PCR. Stool examination revealed 16 cases with C. parvum, and 6 with C. cayetanensis, and 3 cases showed mixed infection. The results were compared with the established nested PCR assay to detect DNA directly from stool specimens. The patients <3 years old more affected by Cryptosporidium infection, unlike Cyclospora sp. Infection was in older age groups, which reflected the modes of parasite' transmission. Diarrheal illness was stronger for Cyclospora than for Cryptosporidium. After the extraction of DNA from stool, a 402-bp fragment of C. parvum, and 602 bp fragment of C. cayetanensis was amplified. The amplified products, 194-bp DNA fragment for C. parvum, and 306 bp DNA fragment of C. cayetanensis were used for the second run. This study indicated that primers were specific for DNA of C. parvum and C. cayetanensis. PCR detected a total of 22 [44.9%] positives for C. parvtim infection [6 negative by AF stool examination], and 12[24.5%] positives for C. cayetanensis. Infection [6 negative by AF stool examination], 7[14.3%] showed mixed infection [4 negative by AF stool examination], all microscopic negative specimens were positive by successive stool examination. Microscopy exhibited sensitivity of 72.7% for C. parvwn, 50% for C. cayetanensis and 100% specificity for both parasites compared to 100% sensitivity and specificity with PCR. So, PCR is more sensitive and easier to interpret but required more hands-on time to perform and is more expensive. However, PCR batch analysis reduces the cost considerably

Vitamin C supplement modulates heat shock protein 72 gene expression in skeletal muscle of rats with type 2 diabetes

Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. In this study we examined the HSP72 gene expression in skeletal muscle of type 2 diabetic rats induced by oral fructose administration [66% of total caloric intake] compared to control and the possibility to increase its level by oral administration of vitamin C [100mg/kg/day for 8 weeks]. The amount of HSP72 m RNA in muscles of diabetic rats was lower than in control non-diabetic group [20.3 +/- 6.37 versus 40.52 +/- 7.49 micro g/g tissue] and its expression increased significantly by vitamin C administration [51.41 +/- 22.54 micro g/g tissue]. There was an insignificant increase in muscle insulin-stimulated glucose uptake after vitamin C administration in diabetic rats [2.59 +/- 0.66mg/g tissue versus 2 +/- 0.7mg/g tissue in diabetics not receiving vitamin C]. The plasma glucose level following vitamin C administration in the diabetic group, showed a significant negative correlation with the expression of HSP72. The concentration of malondialdehyde [MDA] as a measure of lipid peroxidation increased significantly in diabetics [2.019 +/- 0.53 micro mol/g tissue] compared to control group [0.926 +/- 0.19 micro mol/g tissue] and administration of vitamin C in diabetic rats decreased the concentration of MDA insignificantly [1.55 +/- 0.47 micro mol/g tissue] compared to the diabetic group not receiving vitamin C. In conclusion, the finding of decreased levels of HSP72 expression and decreased insulin-stimulated glucose uptake in skeletal muscle of type 2 diabetic rats raises the possibility that heat shock proteins may be involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetics. Administration of vitamin C could be used in diabetics to increase heat shock protein HSP72 expression and to improve insulin resistance

Molecular Characterization of cryptosporidium Parvum isolates obtained from Humans

In this study, 50 stool specimens collected from severe diarrheic patients were examined microscopically for protozoan parasites mainly, Cryptosporidium parvum. Stool examination revealed 22 cases with C. parvum, 8, with E. histolytica, 14 with G. Intestinalis and 6 were parasite-free. The results were compared with the established nested PCR assay to detect DNA directly from stool specimens. After the extraction of DNA from stool, a 402-bp fragment of C. Parvum DNA was amplified with 2 26-mer outer primers. The amplified products, 194-bp DNA fragment, were used for a second run. This study indicated that the used primers are specific for DNA of C. parvum. PCR detected 28 positive cases, 6 of them were negative by AF stool examination, which eventually confirmed to be positive by several successive examinations of the stool and/or duodenal aspiration. Microscopy exhibited 78.5% sensitivity and 100% specificity compared with 100% specificity and sensitivity with PCR. Consequently, it was concluded that PCR is more sensitive and easier to interpret, but required more hands-on time to perform and is more expensive than microscopy. However, PCR batch analysis reduces the cost considerably

Study of whole blood glutathione peroxidase enzyme activity and serum selenium level in bronchial asthma and COPD

This study was carried out in Kasr El-Aini Hospital and included 70 age and sex matched subjects who were divided into three groups. Group I included 25 patients with bronchial asthma, group II included 25 patients with COPD and group III included 20 healthy volunteers. The aim of this work was to study the relation between serum selenium level and whole blood GSH-Px activity and inflammation in bronchial asthma and COPD and if they have a correlation with the severity of the disease. All patients were subjected to history taking, clinical examination, ventilatory pulmonary function test and measurement of serum selenium level and whole blood GSH-Px activity. Serum selenium level and whole blood GSH-Px activity have a role in the pathogenesis of inflammation in bronchial asthma and COPD where they act against the oxidative stress. The reduction of serum selenium level and whole blood GSH-Px activity is correlated with the clinical and functional severity of the disease. Dietary supplementation with selenium and glutathione may have a role in the treatment of bronchial asthma and COPD

adrenergic system in the ischemic heart: evidence for a protective role induced by cardiac gene modulation

Twenty-one rabbits' isolated perfused hearts were used in this study. Animals were divided into three groups. Group 1 [control, non preconditioned group] received no treatment and subjected to ischemia reperfusion protocol designed for all groups. Group 2 [PE group] was preconditioned by alpha-1 adrenoceptor agonist [50 mug/kg phenylephrine [PE]] pretreatment 24 hours before induction of ischemia. Group 3 [PE and Pr group] received alpha-1 adrenergic blocker prazosin [Pr] in a dose of 50 mug/kg 15 minutes prior to administration of PE. 24 hours later, hearts were isolated and perfused in Langendorff mode. All hearts were subjected to 30 minutes of no flow ischemia, followed by 120 minutes reperfusion. The following parameters were measured at base line, during and at the end of 120 minutes reperfusion period: Left ventricular developed pressure [LVDP], heart rate [HR], rate pressure product [RPP], peak rate of maximum left ventricular pressure rise [dP/dTmax] and peak rate of pressure fall [dP/dTmin]. ECG changes were recorded. Expression of iNOS was also detected in left ventricular tissue of all studied groups at the end of reperfusion by reverse transcriptase polymerase chain reaction. Isolated hearts after phenylephrine pretreatment significantly improved post ischemic cardiac performance as indicated by higher: LVDP, HR, RPP, dP/dTmax and dP/dTmin and lower St segment elevation as compared to control group. Increased expression of iNOS mRNA was also demonstrated. Prazocin administration completely abrogated the improved functional recovery observed with PE alone. The phenylephrine induced expression of iNOS mRNA was attenuated when hearts received prazocin