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Biomedical subjects

S A Saeed

Publications and source records attributed to S A Saeed.

At least 37 records · Page 2Linked to original sources
PubMed1998

The inhibitory effect of cinchonine on human platelet aggregation due to blockade of calcium influx.

The Cinchona bark contains alkaloids like quinine, quinidine, cinchonine and cinchonidine. These agents are effective antimalarial drugs and have been used clinically in malaria caused by Plasmodium falciparum. Previous studies show that quinine and quinidine exert effects on cardiovascular system. This study was conducted to examine the effect of cinchonine on human platelet aggregation. The results show that cinchonine inhibited platelet aggregation mediated by platelet agonists, epinephrine (200 microM), ADP (4.3 microM), platelet activating factor (PAF; 800 nM) and collagen (638 nM) but had no effect on arachidonic acid (AA; 0.75 mM). Cinchonine was most effective in inhibiting aggregation induced by platelet activating factor and epinephrine with IC50 values of 125 and 180 microM respectively, however, higher concentrations of cinchonine were required to inhibit aggregation mediated by ADP or collagen (IC50; 300 microM). Pretreatment of platelets with cinchonine inhibited aggregation caused by Ca2+ ionophore, A-23187 (6 microM), in a dose-dependent manner (IC50; 300 microM) indicating an inhibitory effect on Ca2+-signaling cascade. This was supported by measuring [Ca2+]i in platelets loaded with Fura-2AM where cinchonine inhibited the rise in cytosolic Ca2+ mediated by A-23187 (6 microM) or collagen (638 nM). Results show that cinchonine (20 microM) also inhibited aggregation when platelets were pretreated with protein kinase C (PKC) activator, phorbol myristate acetate (PMA; 0.1 microM) in combination with low doses of platelet activating factor (80 nM). Cinchonine, however, had no effect on AA-induced platelet aggregation and thromboxane A2 (TXA2) synthesis in platelets. These results suggest that antiplatelet effects of cinchonine are mediated mainly through inhibition of Ca2+-influx and protein kinase C pathways in platelets.

Adenosine Diphosphate↗
PubMed1998

Panic disorder: effective treatment options.

Panic disorder is a distressing and debilitating condition with a familial tendency; it may be associated with situational (agoraphobic) avoidance. The diagnosis of panic disorder requires recurrent, unexpected panic attacks and at least one of the following characteristics: persistent concern about having an additional attack (anticipatory anxiety); worry about the implications of an attack or its consequences (e.g., a catastrophic medical or mental consequence) and making a significant change in behavior as a consequence of the attacks. A variety of pharmacologic interventions is available, as are non-pharmacologic cognitive or cognitive-behavioral therapies that have demonstrated safety and efficacy in the treatment of panic disorder. Early detection and thoughtful selection of appropriate first-line interventions can help these patients, who often have been impaired for years, regain their confidence and ability to function in society.

Humans↗
PubMed1998

Seasonal affective disorders.

Seasonal affective disorder is a pattern of major depressive episodes that occur and remit with changes in seasons. It may be seen in major depressive or bipolar disorders, as described in the Diagnostic and Statistical. Manual of Mental Disorders (DSM-IV). The most recognized form of seasonal affective disorder, "winter depression," is characterized by recurrent episodes of depression, hypersomnia, augmented appetite with carbohydrate craving, and weight gain that begin in the autumn and continue through the winter months. Physicians have many options for treating seasonal affective disorder. While questions regarding the validity of seasonal affective disorder as a syndrome and the mechanism of action of light therapy continue to be investigated, the established effectiveness of light therapy in patients with winter depression supports the usefulness of assessment for this seasonal pattern and consideration of light therapy as an option in addition to existing treatment choices.

Diagnosis, Differential↗
PubMed1998

An assessment of the potential of protopine to inhibit microsomal drug metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents.

The potential of protopine to inhibit microsomal drug metabolising enzymes (MDM E) and prevent paracetamol- and CCl4-induced hepatotoxicity was studied in rats. Paracetamol at the dose of 640 mg kg-1 produced hepatic damage in rats as manifested by the rise in serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) to 972+/-186 and 624+/-131 IU (mean+/-sem; n=10), respectively, compared to respective control values of 101+/-29 and 64+/-18 IU. Pretreatment of rats with protopine (11 mg kg-1, orally twice daily for 2 days) lowered significantly the respective serum AST and ALT levels (P<0.05) to 289+/-52 and 178+/-43 IU. The hepatotoxic dose of CCl4 (1.5 ml kg-1; orally) raised serum AST and ALT levels to 543+/-89 and 387+/-69 IU (mean+/-sem; n=10), respectively, compared to respective control values of 98+/-28 and 56+/-17 IU. The same dose of protopine (11 mg kg-1) was able to prevent significantly (P<0.05), the CCl4-induced rise in serum enzymes and the estimated values of AST and ALT were 168+/-36 and 93+/-28 IU, respectively. Protopine caused prolongation (P<0.05) in pentobarbital (55 mg kg-1)-induced sleep as well as potentiated strychnine-induced toxicity in rats, suggestive of an inhibitory effect on MDME. These results indicate that protopine exhibits anti-hepatotoxic action which may be mediated through inhibition of MDME.

Acetaminophen↗
PubMed1998

Dual effects of nimesulide, a COX-2 inhibitor, in human platelets.

Nimesulide (CAS 51803-78-2) has been shown to exert marked anti-inflammatory effect in several in vivo models of inflammation. Since nimesulide is considered to be a selective inhibitor of COX-2, it has not been studied in detail in relation to its mechanistic effects on platelets, which express COX-1. This study was conducted to investigate the effects of nimesulide in platelet aggregation. We show that nimesulide (1-100 microM) inhibited platelet aggregation induced by adrenaline (20-200 microM). It also inhibited thromboxane A2 (TXA2) formation by platelets at low concentration (IC50; 1 microM). However, much lower concentrations of nimesulide (0.01-0.1 microM) potentiated the aggregatory response of subthreshold concentrations of adrenaline (0.2-2 microM). Such an effect was blocked by Ca2+-channel blockers, verapamil and diltiazem (IC50: 7 and 46 microM, respectively), nitric oxide donor, SNAP (IC50; 2 microM) and cinchonine (10 nM) but not by genistein (up to 10 microM). These results are indicative of the concentration-dependent dual effects of nimesulide on human platelet aggregation. The synergistic effect of low doses of nimesulide and adrenaline seems to be mediated through inhibition of multiple signalling pathways.

Blood Platelets↗
PubMed1998

Muscarinic regulation of intracellular signaling and neurosecretion in gonadotropin-releasing hormone neurons.

Agonist activation of cholinergic receptors expressed in perifused hypothalamic and immortalized GnRH-producing (GT1-7) cells induced prominent peaks in GnRH release, each followed by a rapid decrease, a transient plateau, and a decline to below basal levels. The complex profile of GnRH release suggested that acetylcholine (ACh) acts through different cholinergic receptor subtypes to exert stimulatory and inhibitory effects on GnRH release. Whereas activation of nicotinic receptors caused a transient increase in GnRH release, activation of muscarinic receptors inhibited basal GnRH release. Nanomolar concentrations of ACh caused dose-dependent inhibition of cAMP production that was prevented by pertussis toxin (PTX), consistent with the activation of a plasma-membrane Gi protein. Micromolar concentrations of ACh also caused an increase in phosphoinositide hydrolysis that was inhibited by the M1 receptor antagonist, pirenzepine. In ACh-treated cells, immunoblot analysis revealed that membrane-associated G(alpha q/11) immunoreactivity was decreased after 5 min but was restored at later times. In contrast, immunoreactive G(alpha i3) was decreased for up to 120 min after ACh treatment. The agonist-induced changes in G protein alpha-subunits liberated during activation of muscarinic receptors were correlated with regulation of their respective transduction pathways. These results indicate that ACh modulates GnRH release from hypothalamic neurons through both M1 and M2 muscarinic receptors. These receptor subtypes are coupled to Gq and Gi proteins that respectively influence the activities of PLC and adenylyl cyclase/ion channels, with consequent effects on neurosecretion.

Acetylcholine↗
PubMed1997

Anti-thrombotic and anti-inflammatory activities of protopine.

The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (microM) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen; 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A2 (TXA2) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg-1) protected rabbits from the lethal effects of AA (2 mg kg-1) or PAF (11 micrograms kg-1) in dose-dependent fashion. Protopine (50-100 mg kg-1) also inhibited carrageenan-induced rat paw oedema with a potency of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties.

Adenosine Diphosphate↗
PubMed1997

The antiplatelet aggregatory activity of Acacia nilotica is due to blockade of calcium influx through membrane calcium channels.

1. The extract of Acacia nilotica (A. nilotica) blocked platelet aggregation mediated by platelet agonists, arachidonic acid (0.75 mM), ADP (4.3 microM), platelet activating factor (800 nM) and collagen (638 nM) in a dose-dependent manner. 2. The extract (0.21-1.4 mg/ml) blocked the platelet aggregation induced by Ca2+ ionophore, A-23187 (6 microM), in a dose-dependent manner, indicating that the Ca2+ influx is involved in aggregation. 3. The plant extract also inhibited aggregation in platelets pretreated with phorbol, 12-myristate, 13-acetate (196 nM) alone or in combination with ADP (4.3 microM), indicating an effect on protein kinase C. 4. These results indicate that the antiplatelet aggregatory activity of the extract of A. nilotica is mainly due to blockade of Ca2+ channels, although evidence also suggests the involvement of protein kinase C.

Acacia↗
PubMed1997

Effects of lipoproteins on cyclo-oxygenase and lipoxygenase pathways in human platelets.

The products of arachidonic acid (AA) metabolism in platelets play an important role in platelet shape change, adhesion and aggregation which may participate in the pathogenesis of ischemic heart disease and thrombosis. Since lipoproteins are also involved in the pathogenesis of thrombo-embolic disorders, the effect of human lipoproteins (HDL, LDL, VLDL) on AA metabolism in human platelets was investigated. Lipoproteins were separated by density gradient zonal ultracentrifugation. The effects of lipoproteins on production of AA metabolites in human platelets i.e., thromboxane A2 (TXA2) and hydroxy-eicosatetraenoic acids (HETEs) were examined using radiometric thin layer chromatography coupled with automated data integrator system. In human platelets, HDL inhibited 12-HETE and TXA2 formation in a concentration-dependent manner. LDL had a strong inhibitory effect on TXA2 production and a weak inhibitory effect on 12-HETE production. VLDL had no effect on platelet AA metabolism. These findings point to a new facet of lipoproteins action and suggest that lipoproteins may have a physiological role in the regulation of AA metabolism in platelets.

Adult↗
PubMed1996

An open trial of fluvoxamine therapy for panic disorder complicated by depression.

BACKGROUND: The efficacy of fluvoxamine in the treatment of panic disorder complicated by depression was investigated in an 8-week, single-group, open-label, flexible-dose trial. METHOD: Seventeen patients having a principal diagnosis of panic disorder and scoring 16 or more on the 17-item Hamilton Rating Scale for Depression were treated with fluvoxamine at a mean final dose of 213 mg/ day. Outcome was assessed on measures of panic attacks, general and anticipatory anxiety, agoraphobic avoidance, depression, disability, and fear of anxiety symptoms. RESULTS: Subjects improved on all measures except agoraphobic avoidance. Thirteen either chose to remain on fluvoxamine treatment after the study ended or resumed taking it after a brief period without medication or on another medication. CONCLUSION: Fluvoxamine appears to be effective in this population.

Adult↗
PubMed1996

Protein kinase C inhibitor, chelerythrine, potentiates the adrenaline-mediated aggregation of human platelets through calcium influx.

The role of protein kinase C (PKC) using its selective inhibitor, chelerythrine, in agonist mediated platelet aggregation was studied. Chelerythrine had no effect on the aggregation induced by adrenaline, PAF, collagen and ADP at the maximum doses of these agonists. However, it potentiated the aggregatory response of low doses of adrenaline (0.4-1 microM). Such an effect was blocked by Ca(++)-channel blockers, verapamil and diltiazem indicating the likely involvement of Ca++ influx in the platelet aggregation during the cascade.

Adrenergic alpha-Agonists↗
PubMed1995

Altered platelet activating factor metabolism in insulin dependent diabetes mellitus.

Diabetes mellitus is associated with several abnormalities of platelet function. Recent studies have shown that the blood level of platelet activating factor (PAF), a potent inducer of platelet aggregation, is elevated in insulin dependent diabetes mellitus (IDDM) and remains unchanged in non-insulin dependent diabetes mellitus (NIDDM) patients. However, the mechanism of this increase in PAF levels has not been determined. In this study we have measured the activity of plasma PAF acetylhydrolase (an enzyme that regulates PAF levels) and lipoprotein levels in control subjects and diabetic patients. The data presented show that plasma PAF acetylhydrolase activity is significantly decreased in IDDM and is not altered in NIDDM patients. The lipoprotein levels were similar in control and diabetic subjects and there was no correlation between lipoprotein levels and PAF acetylhydrolase activity. These results suggest that the elevated levels of PAF in IDDM patients could be due to a decrease in plasma PAF acetylhydrolase activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗