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Biomedical subjects

A Ayub

Publications and source records attributed to A Ayub.

At least 19 recordsLinked to original sources
PubMed2006

Role of the calcarine cortex (V1) in perception of visual cues for saccades.

OBJECTIVE: To determine the initial level at which the pathways for cue perception, saccades and antisaccades diverge. METHODS: Two procedures: single pulse transcranial magnetic stimulation (sTMS) over posterior occiput and backward masking were used. A visual cue directed saccades to the left or right, either a pro-saccade (to the side of the cue but beyond it) or an antisaccade, i.e., contraversive saccade. No visual target was presented. RESULTS: Latencies of the two types of saccades did not differ. Focal sTMS applied unilaterally over V1 suppressed both perception of a cue flashed 80-90ms earlier contralaterally (but not ipsilaterally) and the appropriate saccade. Masking at a delay of 100ms abolished the appropriate saccade and cue perception. CONCLUSIONS: V1 is essential for the perception of a flashed cue and for executing appropriate pro- and contraversive saccades. Masking may occur beyond V1, where the pathways for perception and for saccades at least to the next visual processing level start separating. SIGNIFICANCE: VI is needed for rapid, accurate perceptual and motor responses to the crudest (left versus right) cues. It is unlikely that the "where" system can have a major direct input bypassing V1.

Attention↗
PubMed2001

Downregulation of protein kinase C inhibits activation of mitochondrial K(ATP) channels by diazoxide.

BACKGROUND: The mitochondrial K(ATP) (mitoK(ATP)) channel has been shown to confer short- and long-term cardioprotection against prolonged ischemia via protein kinase C (PKC) signaling pathways. However, the exact association between PKC or its isoforms and mitoK(ATP) channels has not yet been clarified. The present study tested the hypothesis that the activity and translocation of PKC to the mitochondria are important for cardiac protection elicited by mitoK(ATP) channels. Methods and Results-PKC was downregulated by prolonged (24-hour) treatment with phorbol 12-myristate 13-acetate (4 microgram/kg body weight) before subsequent experiments in rats. Langendorff-perfused rat hearts were subjected to 40 minutes of ischemia followed by 30 minutes of reperfusion. Effects of PKC downregulation on the activation of mitoK(ATP) channels and other interventions on hemodynamic, biochemical, and pathological changes were assessed. Subcellular localization of PKC isoforms by Western blot analysis and immunocytochemistry demonstrated that PKC-alpha and PKC-delta were translocated to the sarcolemma and that PKC-delta was translocated to the mitochondria after diazoxide treatment. In hearts treated with diazoxide (80 micromol/L), a significant improvement in cardiac function and an attenuation of cell injury were observed. In PKC-downregulated hearts, protection was abolished because mitoK(ATP) channels could not be activated by diazoxide. CONCLUSIONS: These data suggest that PKC activation is required for the opening of mitoK(ATP) channels during protection against ischemia and that this effect is linked to isoform-specific translocation of PKC-delta to the mitochondria.

Adenosine Triphosphate↗
PubMed2001

Mitochondrial K(ATP) channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide.

Nitric oxide (NO) has been implicated in the "second-window" of ischemic preconditioning (PC). However, the identity of the end effector after initiation of preconditioning by NO is not known. It is likely that NO is involved in opening of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. We hypothesized that NO is an important trigger for the opening of mitoK(ATP) channels in the late phase of preconditioning and inducible nitric oxide synthase (iNOS) up-regulation via NF kappa B plays a critical role in diazoxide-induced cardioprotection. To examine this, diazoxide (7 mg/kg) was administered to wild-type (WT) mice and mice lacking the gene 24 hours before 40 minutes of global ischemia. Hearts were perfused in a Langendorff mode and effects of activation of mitoK(ATP) channel and other interventions on functional, biochemical and pathological changes in ischemic hearts were assessed. In hearts from WT mice treated diazoxide, left-ventricular-developed pressure, end-diastolic pressure and coronary flow were significantly improved after ischemia/reperfusion (I/R); lactate dehydrogenase (LDH) release was also significantly decreased, while ATP contents were significantly higher. Administration of 5-HD, a specific blocker of mitoK(ATP) channel or l -NAME, an inhibitor of iNOS before I/R, during diazoxide-pretreatment completely blocked the late cardioprotection against ischemia. Late cardioprotection was also blocked by inhibition of either PKC- delta by rottlerin or NF kappa B by DDTC before diazoxide pretreatment. Diazoxide pretreatment significantly increased nuclear translocation of p65 which was blocked by protein kinase C (PKC) or nitric oxide synthase (NOS) inhibition. Diazoxide was totally inefffective in iNOS knockout mice. These results suggest that diazoxide activates NF kappa B via PKC signaling pathway and that leads to iNOS up-regulation after 24 hours. NO which is generated upon ischemic stress triggers the opening of mitoK(ATP)channel as an end effector of cardioprotection during late PC.

Acetophenones↗
PubMed2001

Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis.

We tested the hypothesis whether calcium preconditioning (CPC) reduces reoxygenation injury by inhibiting mitochondrial permeability transition (MPT). Cultured myocytes were preconditioned by a brief exposure to 1.5 mM calcium (CPC) and subjected to 3 h of anoxia followed by 2 h of reoxygenation (A-R). Myocytes were also treated with 0.2 microM/l cyclosporin A (CsA), an inhibitor of MPT, before A-R. A significant increase of viable cells and reduced lactate dehydrogenase release was observed both in CPC- and CsA-treated myocytes compared with the A-R group. Cytochrome c release was predominantly observed in the cytoplasm of myocytes in the A-R group in contrast with CPC- or CsA-treated groups, where it was restricted only to mitochondria. Similarly, the cell death by apoptosis was also markedly attenuated in these groups. Electron-dense Ca(2+) deposits in mitochondria were also less frequent. Atractyloside (20 microM/l), an adenine nucleotide translocase inhibitor, caused changes similar to those in the A-R group, suggesting a role of MPT in A-R injury. Protection by inhibition of MPT by CsA and CPC suggests that MPT plays an important role in reoxygenation/reperfusion injury. The data further suggest that preconditioning inhibits MPT by inhibiting Ca(2+) accumulation by mitochondria.

Animals↗
PubMed2001

Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.

Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed DeltaPsi(m), as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome c immunostaining. Activation of mitoK(ATP) channel with diazoxide (100 micromol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized DeltaPsi(m). This protection was blocked by 5-hydroxydecanoate (500 micromol/l), a mitoK(ATP) channel-selective inhibitor, but not by HMR-1098 (30 micromol/l), a putative sarcolemmal K(ATP) channel-selective inhibitor. Dissipation of DeltaPsi(m) also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts DeltaPsi(m) and induces apoptosis, which are prevented by the activation of the mitoK(ATP) channel. This further emphasizes the therapeutic significance of mitoK(ATP) channel agonists in the prevention of ischemia-reperfusion cell injury.

Animals↗
PubMed1999

Low serum paraoxonase: a risk factor for atherosclerotic disease?

Serum paraoxonase (PON1) hydrolyses organophosphate (OP) insecticides and nerve gases and is responsible for determining the selective toxicity of these compounds in mammals. PON1 has two genetic polymorphisms giving rise to amino acid substitutions at position 55 and 192. The 192 polymorphism is the major determinant of the PON1 activity polymorphism towards organophosphates. However, the 55 polymorphism also modulates activity. PON1 also may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification perhaps by hydrolysing phospholipid-hydroperoxides. The PON1 polymorphisms are important in determining the capacity of high-density lipoprotein (HDL) to protect low-density lipoprotein (LDL) against oxidative modification in vitro and this may explain the relationship between the PON1 alleles and coronary heart disease in case-control studies.

Animals↗
PubMed1999

Serum paraoxonase after myocardial infarction.

HDL has been shown to prevent the oxidative modification of LDL. The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Human serum paraoxonase (PON1) is closely associated with a specific HDL subfraction also containing apoA1 and clusterin. Recently PON1 has been implicated in the pathogenesis of atherosclerosis. We have examined the activity, concentration, and specific activity of PON1 in 50 patients on admission to hospital immediately after acute myocardial infarction (MI) and in 48 age- and gender-matched controls. Serum PON1 activity and concentration were significantly lower in patients with MI than in controls (activity, 221.5 [99.3 to 303.2] nmol. min-1. mL-1 in controls and 130.1 [78.9 to 230.3] nmol. min-1. mL-1 in MI patients [P<0.05]; concentration, 95.7 [73.2 to 135.5] microg/mL in controls and 35.4 [21.6 to 51.3] microg/mL in MI patients [P<0.001]). PON1-specific activity was significantly higher in patients with MI than in controls (1.5 [0.9 to 2.9] versus 3.4 [2.0 to 8.5] nmol. min-1. microg-1 [P<0.001]) due to the much lower PON1 concentration. PON1 activity had risen significantly (P<0.05) to 158.1 (85.4 to 282.0) nmol. min-1. mL-1 at day 42 but was still significantly less than that of controls. No significant variation in PON1 concentration occured in the days after MI or at 6 weeks. Also, no significant variation in specific activity was seen after MI. When the patients were divided into subgroups based on whether or not they received thrombolytic therapy on admission to hospital, no significant difference in PON1 levels was observed. Serum HDL cholesterol in patients with MI on admission was not significantly different than in controls, and the decrease that occurred by the fifth day after MI did not explain the lower PON1 levels. We conclude that low serum PON1 activity in patients with MI may be a consequence of the coronary event itself or could have been present before MI. The low PON1 activity was also not explicable on the basis of PON1 genotypes because the prevalence of genotypes associated with low activity was not sufficient to explain fully the difference in activity levels between patients and controls. The explanation for the low PON1 activity was most likely a decrease in serum PON1 concentration. The importance of PON1 as a predictive risk factor for MI should be assessed in future studies.

Aryldialkylphosphatase↗
PubMed1994

Idiopathic chronic active hepatitis: a diagnostic and therapeutic dilemma.

A 56-year-old Saudi male was admitted with abnormal liver chemistry values and a > 5-month history of lethargy, malaise, anorexia, and jaundice. Extensive investigations did not establish an etiological diagnosis. Liver histology confirmed the clinically apparent aggressive hepatitis with fibrosis but gave no clue to its etiology. The patient was empirically treated with alpha-interferon for presumed non-A, non-B hepatitis, with clinical and biochemical worsening. Interferon was discontinued and the patient was started on immunosuppression. Dramatic clinical and biochemical improvement occurred, with normalization of the liver chemistry within 4 weeks. The patient has been followed-up for 12 months and has not suffered a relapse. This case highlights the etiological heterogeneity of chronic active hepatitis. The entity of autoimmune chronic active hepatitis is unclear, and perhaps it is better defined as steroid-responsive hepatitis. Steroid-responsive hepatitis should always be considered in cases of cryptogenic chronic active hepatitis.

Autoimmune Diseases↗
PubMed1993

Brucella peritonitis.

We report the case of a patient with peritonitis caused by Brucella melitensis who also had chronic liver disease. At first the patient was treated for bacterial peritonitis but when a lymphocytic ascites was aspirated antituberculosis chemotherapy was given. However, the serological tests for brucellosis were strongly positive and subsequently B. melitensis was isolated from ascitic fluid.

Anti-Bacterial Agents↗
PubMed1993

Chronic non-A, non-B hepatitis complicated by end-stage renal failure treated with recombinant interferon alpha.

Chronic non-A, non-B hepatitis occurs in 50% of Saudi patients with end-stage renal failure and requires long-term hemodialysis since it is a contraindication to renal transplantation. Thirteen patients with biochemical and histological documented chronic non-A, non-B hepatitis (11 with HCV antibodies) entered a double-blind placebo controlled cross-over study, in which Roferon A 3 MU or placebo were administered subcutaneously 3 times weekly after hemodialysis for 6 months. The mean ALT fell significantly from pretreatment levels of 74.7 (95% confidence interval (CI) 54.7, 92.5) (13 patients in the 6-month run-in period) and 66.8 (CI 47.7, 85.8) (7 patients in the run-in period + 6 patients in the placebo period) (difference NS) to 37.6 (CI 21.0, 54.2) during interferon treatment (P < 0.005). In 10/13 patients (77%) ALT levels became normal. In the 6-month follow-up period immediately after therapy, the mean ALT was 45.2 (CI 28.0, 62.0). Although this change was not significant (P = 0.49), only 7 of these 10 patients sustained biochemical remission in the 6-month follow-up period. The corresponding total Histological Activity Index improved from 8.9 (CI 7.5, 10.3), 8.9 (CI 7.2, 10.7) (difference NS) to 6.2 (CI 3.9, 8.5) (P < 0.05; P = 0.052, respectively). Intralobular inflammation and periportal inflammation showed the most significant changes. Five of 13 (39%) and 2/13 patients (15%) had complete resolution of piecemeal necrosis and intralobular inflammation, respectively. Toxic effects of interferon were mild, early and self-limiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Histologically advanced chronic hepatitis C treated with recombinant alpha-interferon: a randomized placebo-controlled double-blind cross-over study.

Chronic hepatitis C is common in Saudi Arabia and most often presents in an advanced stage. To assess the response of patients to interferon, a randomized placebo-controlled double-blind study was undertaken. All but 1 patient had cirrhosis or fibrosis before interferon. After a 24-week observation period patients received alpha 2a interferon, 3 mega units sc tiw or placebo for 24 weeks, then the opposite treatment for another 24 weeks followed by 24 weeks of observation. Liver biopsies were performed before and after each of the treatment phases. Twenty-two out of 24 patients completed the study. The mean alanine aminotransferase (ALT) levels fell from 150.7 +/- 118.7 units/l to 91.0 +/- 42.6 units/l after 6 months interferon treatment (P = 0.03) but only 3 patients (14%) had complete normalization of mean ALT levels and 4 (18%) had > 50% reduction. The mean hepatitis activity index fell from 12.2 +/- 2.6 immediately before to 11.6 +/- 2.5 just after interferon (P = 0.4). After interferon there was an insignificant raise in 6-month mean ALT. Hepatitis C virus-RNA was positive in all 17 patients tested and remained so after treatment. Side-effects were mild and well tolerated. Alpha interferon 3 mega units tiw for 24 weeks is not an effective treatment of histologically advanced chronic hepatitis C.

Adult↗
PubMed1993

Primary hepatic vipoma.

A 35-yr-old male presented with a 3-yr history of voluminous watery diarrhea. He had episodes of severe generalized weakness which responded to fluid and electrolyte replacement therapy. Investigations revealed a solitary liver mass and an elevated vasoactive intestinal polypeptide level. An extensive work-up did not show any other extrahepatic primary lesion. Surgical resection ameliorated all of his symptoms, accompanied by a decrease in the vasoactive intestinal polypeptide level. We believe that this patient represents a case of primary hepatic vipoma syndrome. To our present knowledge, this has not been reported previously. We discuss the clinical manifestations, investigations, and management of the case.

Adult↗
PubMed1981

Encephalopathy following jejunoileostomy.

A neurological syndrome characterized by episodes of confusion, slurred speech, and unsteadiness is described in patients who have undergone jejunoileostomy for obesity. This syndrome has been noted in seven of 110 patients studied, although it may be more common. It appears to subside spontaneously or may respond to oral food restriction, with or without intravenous fluid plus vitamins and minerals. Episodes tend to recur in a given patient. Reversible changes in the EEG have been observed. Pertinent clinical and laboratory findings are described but no definite etiologic factor has been identified. The possible mechanisms involved in this syndrome of metabolic encephalopathy following jejunoileostomy are discussed.

Adult↗
PubMed1979

Gallstones, obesity, and jejunoileostomy.

An attempt has been made to identify the causes of increased cholesterol gallstone formation in obese patients both before and following jejunoileostomy. The prime lithogenic mechanism in obesity seems to be increased cholesterol mobilization and excretion in the bile. In jejunoileal bypass, a host of factors, including possible limited bile salt synthesis, increased bile salt loss, and bacterial alteration of bile acids, along with the effects of rapid weight loss, may play a role. The identification and understanding of these factors will be important if attempts at prevention by administratin of antibiotics to reduce bacterial overgrowth, or by giving chenodeoxycholic or ursodeoxycholic acid to replenish the diminished bile acid pools, are to be carried out.

Bile Acids and Salts↗
PubMedDate not supplied

Anti-Brucella activity of Ro 23-9424, a dual-action antibacterial.

The in vitro activity of dual-acting antibacterial Ro 23-9424 was determined by the agar dilution method against 126 clinical isolates of Brucella melitensis. It was compared with fleroxacin, ciprofloxacin and five conventional drugs. MIC50 and MIC90 for Ro 23-9424 were 1.0 and 4.0 mg/l, respectively, as compared with 0.25 and 0.5 mg/l for fleroxacin and ciprofloxacin. One strain which was resistant to other fluoroquinolones, with an MIC of > 8.0 mg/l, did not show cross-resistance to Ro 23-9424 and had an MIC of 4.0 mg/l. All the strains were susceptible to conventional drugs like gentamicin, streptomycin rifampicin, tetracycline and trimethoprim-sulfamethoxazole, with MICs ranging between 0.12 and 2.0 mg/l. Ro 23-9424 did not exhibit in vitro synergy with any of the conventional drugs.

Anti-Infective Agents↗