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Pioglitazone (Pio) and swimming exercise (SE) are insulin sensitisers. This investigation was suggested because of the significant side effects associated with Pio treatment in metabolic syndrome (MetS). This study was, therefore, designed to investigate the preventive role of Pio treatment and SE in terms of efficiency and pathological changes in MetS in a rat model. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) control group (C), (ii) exercised control group (C+E), (ill) Pio-treated control group (C+Pio), (iv) group with MetS, (v) group with MetS treated with Pio (MetS+Pio), and (vi) exercised MetS group (MetS+E). Systolic blood pressure and heart rate were measured at the end of the experiments (16 weeks). Retro- orbital blood samples were used to determine the serum levels of glucose, insulin, lipids, gamma glutamyl transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A, and adiponectin. Semiquantitative reverse transcriptase PCR insulin gene expression assays and hepatic histopathological examination were conducted. Swimming exercise significantly improved all of the aforementioned parameters, more so than the Pio treatment. In particular, the serum hepatic enzyme levels and hepatic histopathological changes were improved compared with the MetS group. These results suggested that swimming exercise might be an alternative physiological preventive tool against hepatic dysfunction to avoid the side effects associated with Pio treatment, and this could be demonstrated in a rat model of metabolic syndrome. Key words: metabolic syndrome, pioglitazone, swimming exercise, adiponectin, semiquantitative RT-PCR for insulin gene expression. Resume : Le pioglitazone (Pio) et la natation sont des sensibilisateurs a l'insuline. Cette recherche a ete suggeree par les effets secondaires significatifs associes au traitement du syndrome metabolique par le Pio. Cette etude a ete concue afin d'examiner le role preventif du traitement au Pio et de la natation en termes d'efficacite et de changements pathologiques dans un modele de syndrome metabolique (SM) chez le rat. Soixante rats Sprague-Dawley males ont ete repartis en 6 groupes egaux : (i) controle (C), (ii) controle et exercice (CE), (iii) controle et traitement au Pio (C+Pio), (iv) SM, (v) SM+Pio et (vi) SM+E. A la fin du protocole experimental (16 semaines), la pression sanguine systolique et le rythme cardiaque ont ete determines. Les echantillons sanguins retro-orbitaux ont ete utilises afin de mesurer le glucose, l'insuline, le lipogramme, la gamma glutamyl transferase, l'alanine transaminase, l'aspartate transaminase, la phosphatase alcaline, la fetuine A, et l'adiponectine du serum. Des dosages de l'expression genique de l'insuline par RT-PCR semi-quantitative et un examen histopathologique du foie ont ete realises. La natation ameliorait significativement les parametres mentionnes plus haut et ce, plus efficacement que le traitement au Pio, notamment le niveau serique des enzymes hepatiques et les changements histopathologiques hepatiques comparativement au groupe SM. Ces resultats ont suggere que la natation pouvait constituer un outil physiologique alternatif de prevention de la dysfonction hepatique lors du syndrome metabolique, lors d'une etude visant a eviter les effets secondaires associes au traitement au Pio. [Traduit par la Redaction] Mots-cles: syndrome metabolique, pioglitazone, natation, adiponectine, RT-PCR semi-quantitative de l'expression genique d'insuline., Introduction Metabolic syndrome (MetS) is a major global health problem associated with obesity that affects different organs, especially the key metabolic organs such as the liver (Grundy 2008). Nonalcoholic fatty [...]

Context: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia. Objective: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats. Materials and methods: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups (n=8 rats/group) as control, controlþEA, controlþEAþCC an AMPK inhibitor), T1DM, T1DMþEA, and T1DMþEAþCC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily. Results: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-a (62%), and IL-6 (57.2%) and the nuclear activity of NF-jB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARa (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC. Discussion and conclusions: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine. [ABSTRACT FROM AUTHOR]

This study evaluated the protective effect of resolvin D1 (RVD1) against cadmium chloride (CdCl2)‐induced hippocampal damage and memory loss in rats and investigated if such protection is mediated by modulating the PTEN/PI3K/Akt/mTOR pathway. Adult male Wistar rats (n = 18/group) were divided as control, control + RVD1, CdCl2, CdCl2 + RVD1 and CdCl2 + RVD1 + bpV(pic), a PTEN inhibitor. All treatments were conducted for 4 weeks. Resolvin D1 improved the memory function as measured by Morris water maze (MWM), preserved the structure of CA1 area of the hippocampus, and increased hippocampal levels of RVD1 in the CdCl2‐treated rats. Resolvin D1 also suppressed the generation of reactive oxygen species (ROS), tumour necrosis factor‐α and interleukine‐6 (IL‐6), inhibited nuclear factor κB (NF‐κB) p65, stimulated levels of glutathione (GSH), manganese superoxide dismutase (MnSOD), and Bcl2 but reduced the expression of Bax and cleaved caspase 3 in hippocampi of CdCl2‐treated rats. Concomitantly, it stimulated levels and activity of PTEN and reduced the phosphorylation (activation) of PI3K, Akt and mTOR in hippocampi of CdCl2‐treated rats. In conclusion, RVD1 attenuates CdCl2‐induced memory loss and hippocampal damage in rats mainly by activating PTEN‐induced suppression of PI3K/Akt/mTOR, an effect that seems secondary to its' anti‐oxidant and anti‐inflammatory potential. [ABSTRACT FROM AUTHOR]

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg−1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1β, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi. [ABSTRACT FROM AUTHOR]

Context: Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear. Objective: To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway. Materials and methods: Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 µg/kg) was administered for 21 days, starting one-day post-MI. Results: Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser338), phospho-MEK1/2 (Ser217/221), phospho-ERK1/2 (Thr202/Tyr204), and of their downstream target p-BAD (Ser112) and inhibited the cleavage of caspase-3. Concomitantly, ghrelin prevented the increases in the levels of fibrotic markers, including α-smooth muscle actin (α-SMA), metalloproteinase-9 (MPP-9), and type III collagen. Conclusion: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling. [ABSTRACT FROM AUTHOR]

Objective: To determine the problems related to renal colic due to urinary stones during pregnancy, and the principles of management of those patients in our hospitals. Material and Methods: It is a retrospective analysis of a series of 21 cases of renal colic due to urinary stones during pregnancy from March 2008 to April 2010 at Prince Rashid Ben Al-Hassan Military Hospital, Jordan. Presenting symptoms, diagnostic studies and management of renal stone were evaluated. Results: There were 15,824 deliveries during this period in our study. 21 of them had renal colic due to urinary stones during pregnancy, with an overall incidence in this series of 0.13%. Most of them were in the third trimester of pregnancy followed by the second trimester and the least were in the first trimester. The most common complaints were lank pain (95.2 %), urinary symptoms (hematuria, dysuria and urgency) in 80.9%, nausea and vomiting in 14.3% and fever in 28.6 %. Spontaneous passing of stones was noted in 19 cases (90.5%) with conservative treatment. Two patients were unresponsive or relapsing after medical treatment and were treated surgically in the urological department by double J stents insertion, but no maternal or fetal loss was noted. Conclusion: The majority of cases of renal colic due to urinary stones during pregnancy can be safely managed conservatively. The commonest presenting symptoms in our study were lank pain, urinary symptoms (hematuria, dysuria and urgency), and early surgical intervention resulted in safe maternal and fetal outcome. [ABSTRACT FROM AUTHOR]

Context: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia., Objective: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats., Materials and Methods: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups ( n  = 8 rats/group) as control, control + EA, control + EA + CC an AMPK inhibitor), T1DM, T1DM + EA, and T1DM + EA + CC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily., Results: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-α (62%), and IL-6 (57.2%) and the nuclear activity of NF-κB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARα (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC., Discussion and Conclusions: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Aim: Myocardial infarction (MI) due to sudden occlusion of a major coronary artery leads to a complex series of events that result in left ventricle (LV) impairment eventual heart failure. Therapeutic options are limited to reverse such trends post MI. The aim of this study was to compare the acute cardioprotective effects of the antioxidants, resveratrol (RES) and coenzyme Q10 (CoQ10), either individually or in combination, on infracts size, LV hemodynamics, inflammation and oxidative stress markers in rats with experimentally induced MI., Methods: Male Wistar rats were randomly divided into six groups: control without surgery, sham without occlusion, MI without antioxidants, RES pre-treated then MI (20 mg/kg, orally), CoQ10 then MI (20 mg/kg, intramuscular.), and combined RES and CoQ10 then MI with (each group n = 10). Pretreatment commenced 7 days prior to the permanent occlusion of the left anterior descending (LAD) coronary artery. Infarct area, hemodynamics, inflammation and oxidative stress markers were assessed 24 hours post-MI., Results: Compared to RES alone, CoQ10 pre-administration either by itself or in combination with RES, significantly reduced LV infarct area (57%), and normalized LV hemodynamic parameters like LVEDP (100%), LVSP (95.4%), LV +dp/dt and -dp/dt (102 and 73.1%, respectively). CoQ10 also decreased serum levels of brain natriuretic peptide (70%), and various circulating inflammatory markers like TNF-α (83.2%) and IL-6 (83.2%). Regarding oxidative stress, TBARS scores were lowered with a concurrent increase in both superoxide dismutase and glutathione peroxidase activities with CoQ10 alone or in combination with RES., Conclusion: Coenzyme Q10 protects against the acute sequelae of myocardial infarction. It profoundly reduced infarct area, inflammation and oxidative stress while normalizing LV hemodynamics post MI.