Ramadhan Oruch - Academia.edu (original) (raw)

Papers by Ramadhan Oruch

Nutrients

Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lip... more Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lipids, and proteins. It does so by facilitating glucose influx from the circulation into the liver, adipose tissue, and skeletal myocytes. The outcome of which is subjected to glycogenesis in skeletal muscle and lipogenesis in adipose tissue, as well as in the liver. Therefore, insulin has an anabolic action while, on the contrary, hypoinsulinemia promotes the reverse process. Protein breakdown in myocytes is also encountered during the late stages of diabetes mellitus. The balance of the blood glucose level in physiological conditions is maintained by virtue of the interactive functions of insulin and glucagon. In insulin resistance (IR), the balance is disturbed because glucose transporters (GLUTs) of cell membranes fail to respond to this peptide hormone, meaning that glucose molecules cannot be internalized into the cells, the consequence of which is hyperglycemia. To develop the full ...

Journal of Chemical Biology, 2009

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processe... more Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs' intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A 2 (PLA 2) and polyphosphoinositide (PPI) metabolism in thrombinstimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA 2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA 2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects.

European Journal of Pharmacology, 2014

A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is at... more A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is attributed to the fact that the precise pathophysiology of this ailment is unclear though a genetic factor is an essential element in etiology. Dissimilar to other serious psychiatric categories such as psychoses and major depression the forecast of this disease is unpredictable. There is a high suicidal risk among BD affected individuals. In this review we will consider lithium, the drug of choice in treatment of this disorder with special emphasis on pharmacology and toxicity. We have also elucidated the alternatives to lithium, since it has a wide spectrum of side-effects. Lithium is known to interact with many types of drugs used to treat different ailments in humans. This could cause either augmentation or minimization of the therapeutic action, causing secondary undesired effects of the agent. This necessitates a search for other alternatives and/or different combinations to lithium in order to decrease the range of unwanted effects for which it has received discredit. These alternatives should be potent mood stabilizers as monotherapy so as to avoid polypharmacy. If not, one should find the best combination of drugs (synergistic agents) such that the lithium dose can be minimized, thereby securing a more potent drug therapy. This study also focuses on the provision of instruction to psychiatric care givers, such as junior doctors in residency, nurses in psychiatric units, psychiatric emergency personnel and, additionally, medical and pharmacy students.

Journal of Chemical Biology, 2010

Chemistry and Physics of Lipids, 2007

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2008

Saudi Medical Journal, 2008

To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), cl... more To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets. This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain (MLC) phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus. All drugs reduced arachidonate liberation with the rank...

Saudi medical journal, 2008

OBJECTIVE To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine... more OBJECTIVE To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets. METHODS This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain (MLC) phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus. RESULTS All drugs reduced arachidonat...

International Journal of Pharmacology

Neuropsychiatric disease and treatment, 2017

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mai... more Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent...

Journal of Bioanalysis & Biomedicine, 2015

The differences in types of psychoses, the suboptimal therapeutic response of psychotic individua... more The differences in types of psychoses, the suboptimal therapeutic response of psychotic individuals to antipsychotics, the variation of the therapeutic effects of the same antipsychotic on different individuals with the same disease, resistance to treatment, relapses despite completing a course of antipsychotic treatment, and the broad spectrum of side-effects of antipsychotics including the most recently designed ones, are pivotal factors necessitating the discovery of new antipsychotic agents. These should be therapeutically potent, efficient in monotherapy and devoid of known dangerous adverse effects that antipsychotics are blamed for. In this comparative review we elucidate two antipsychotic drugs, namely haloperidol and clozapine (typical and atypical antipsychotic agents, respectively) and discuss both their advantages and disadvantages. Because the pathogenesis of psychoses is not yet fully understood, and the prevention of psychoses is almost impossible rather being a myth, the search for the so called ideal, or the near-ideal, antipsychotic agent will continue. Based on this we propose the design of a “hybrid structure” having the desired properties of haloperidol and clozapine, with the intention being to find an optimal antipsychotic agent that exerts efficient therapeutic effects against both positive and negative symptoms of psychosis causing least possible side effects, such as in monotherapy.

In biological systems, there is an equilibrium state between pro-oxidant processes and antioxidan... more In biological systems, there is an equilibrium state between pro-oxidant processes and antioxidant defence systems. If this state is disturbed in favour of pro-oxidant processes, oxidative stress will occur, the consequence of which is increased production of free radicals. Oxidative stress, no matter what its cause, can ultimately result in cell toxicity. Free radicals attack cellular components indiscriminately including lipids, carbohydrates and macromolecules such as proteins and DNA and thus affect their functionality. Lipids, by virtue of their location in cell membranes, are particularly vulnerable to free radical attack and lipid peroxides are produced as a consequence. Membrane stabilization (integrity) is a mandatory issue for survival of any biological system. Vitamin E, the lipid soluble essential micronutrient, embedded within membranes, has a high degree of scavenging activity. It is a highly efficient lipid-soluble chain-breaking antioxidant that has the function of m...

Background: Postmenopausal hypertension is one of the leading causes of morbidity and mortality i... more Background: Postmenopausal hypertension is one of the leading causes of morbidity and mortality in women. Exercise training has been proved to decrease its risk factors and cardiovascular events. Aerobic exercise training stimulates endothelial nitric oxide release that acts as an antithrombotic and is cardiovascular protective. The effect of aerobic exercise training on postmenopausal hypertension is not fully elucidated. The purpose of the study: to investigate the effects of moderate exercise training on nitric oxide levels in postmenopausal hypertension. Methods: A prospective, randomized, controlled trial was conducted on 30 postmenopausal women involved in this study. The participants had at least one year's history of postmenopausal hypertension. Their ages ranged (40-50) years. Their body mass index ranged (30-36 Kg/m 2). They were divided into two equal groups (treatment and control). Nitric oxide levels and blood pressure were measured in both groups in the initial exa...

Quetiapine is an antipsychotic drug that belongs to the group of nonconventional agents. Mainly u... more Quetiapine is an antipsychotic drug that belongs to the group of nonconventional agents. Mainly used to treat schizophrenia, bipolar depressive disorder, and exacerbations of manic and depressive episodes of this condition. It is also used to prevent these episodes of exacerbation, beside its many off-label uses. Atypical antipsychotics treat negative symptoms of psychosis without causing extra sedation, and help schizophrenics to integrate into society and, in addition, to remove unwanted extrapyramidal symptoms that conventional agents are known to exert. Unfortunately, these agents, including quetiapine, have other drawbacks the most serious of which are those associated with the disease spectrum of metabolic syndrome and, furthermore, the many interactions quetiapine may be involved in with other drugs in cases of polypharmacy. This review gives an update on quetiapine and provides a guideline to psychiatric caregivers, and importantly, undergraduates of medicine and pharmacy students on clinical uses (both dedicated and off-label), pharmacology, pharmacopeia, and intoxication that might occur following its use, and how to treat such a condition.

Journal of Chemical Biology, 2009

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processe... more Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than ...

Nutrients

Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lip... more Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lipids, and proteins. It does so by facilitating glucose influx from the circulation into the liver, adipose tissue, and skeletal myocytes. The outcome of which is subjected to glycogenesis in skeletal muscle and lipogenesis in adipose tissue, as well as in the liver. Therefore, insulin has an anabolic action while, on the contrary, hypoinsulinemia promotes the reverse process. Protein breakdown in myocytes is also encountered during the late stages of diabetes mellitus. The balance of the blood glucose level in physiological conditions is maintained by virtue of the interactive functions of insulin and glucagon. In insulin resistance (IR), the balance is disturbed because glucose transporters (GLUTs) of cell membranes fail to respond to this peptide hormone, meaning that glucose molecules cannot be internalized into the cells, the consequence of which is hyperglycemia. To develop the full ...

Journal of Chemical Biology, 2009

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processe... more Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs' intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A 2 (PLA 2) and polyphosphoinositide (PPI) metabolism in thrombinstimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA 2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA 2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects.

European Journal of Pharmacology, 2014

A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is at... more A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is attributed to the fact that the precise pathophysiology of this ailment is unclear though a genetic factor is an essential element in etiology. Dissimilar to other serious psychiatric categories such as psychoses and major depression the forecast of this disease is unpredictable. There is a high suicidal risk among BD affected individuals. In this review we will consider lithium, the drug of choice in treatment of this disorder with special emphasis on pharmacology and toxicity. We have also elucidated the alternatives to lithium, since it has a wide spectrum of side-effects. Lithium is known to interact with many types of drugs used to treat different ailments in humans. This could cause either augmentation or minimization of the therapeutic action, causing secondary undesired effects of the agent. This necessitates a search for other alternatives and/or different combinations to lithium in order to decrease the range of unwanted effects for which it has received discredit. These alternatives should be potent mood stabilizers as monotherapy so as to avoid polypharmacy. If not, one should find the best combination of drugs (synergistic agents) such that the lithium dose can be minimized, thereby securing a more potent drug therapy. This study also focuses on the provision of instruction to psychiatric care givers, such as junior doctors in residency, nurses in psychiatric units, psychiatric emergency personnel and, additionally, medical and pharmacy students.

Journal of Chemical Biology, 2010

Chemistry and Physics of Lipids, 2007

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2008

Saudi Medical Journal, 2008

To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), cl... more To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets. This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain (MLC) phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus. All drugs reduced arachidonate liberation with the rank...

Saudi medical journal, 2008

OBJECTIVE To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine... more OBJECTIVE To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets. METHODS This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain (MLC) phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus. RESULTS All drugs reduced arachidonat...

International Journal of Pharmacology

Neuropsychiatric disease and treatment, 2017

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mai... more Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent...

Journal of Bioanalysis & Biomedicine, 2015

The differences in types of psychoses, the suboptimal therapeutic response of psychotic individua... more The differences in types of psychoses, the suboptimal therapeutic response of psychotic individuals to antipsychotics, the variation of the therapeutic effects of the same antipsychotic on different individuals with the same disease, resistance to treatment, relapses despite completing a course of antipsychotic treatment, and the broad spectrum of side-effects of antipsychotics including the most recently designed ones, are pivotal factors necessitating the discovery of new antipsychotic agents. These should be therapeutically potent, efficient in monotherapy and devoid of known dangerous adverse effects that antipsychotics are blamed for. In this comparative review we elucidate two antipsychotic drugs, namely haloperidol and clozapine (typical and atypical antipsychotic agents, respectively) and discuss both their advantages and disadvantages. Because the pathogenesis of psychoses is not yet fully understood, and the prevention of psychoses is almost impossible rather being a myth, the search for the so called ideal, or the near-ideal, antipsychotic agent will continue. Based on this we propose the design of a “hybrid structure” having the desired properties of haloperidol and clozapine, with the intention being to find an optimal antipsychotic agent that exerts efficient therapeutic effects against both positive and negative symptoms of psychosis causing least possible side effects, such as in monotherapy.

In biological systems, there is an equilibrium state between pro-oxidant processes and antioxidan... more In biological systems, there is an equilibrium state between pro-oxidant processes and antioxidant defence systems. If this state is disturbed in favour of pro-oxidant processes, oxidative stress will occur, the consequence of which is increased production of free radicals. Oxidative stress, no matter what its cause, can ultimately result in cell toxicity. Free radicals attack cellular components indiscriminately including lipids, carbohydrates and macromolecules such as proteins and DNA and thus affect their functionality. Lipids, by virtue of their location in cell membranes, are particularly vulnerable to free radical attack and lipid peroxides are produced as a consequence. Membrane stabilization (integrity) is a mandatory issue for survival of any biological system. Vitamin E, the lipid soluble essential micronutrient, embedded within membranes, has a high degree of scavenging activity. It is a highly efficient lipid-soluble chain-breaking antioxidant that has the function of m...

Background: Postmenopausal hypertension is one of the leading causes of morbidity and mortality i... more Background: Postmenopausal hypertension is one of the leading causes of morbidity and mortality in women. Exercise training has been proved to decrease its risk factors and cardiovascular events. Aerobic exercise training stimulates endothelial nitric oxide release that acts as an antithrombotic and is cardiovascular protective. The effect of aerobic exercise training on postmenopausal hypertension is not fully elucidated. The purpose of the study: to investigate the effects of moderate exercise training on nitric oxide levels in postmenopausal hypertension. Methods: A prospective, randomized, controlled trial was conducted on 30 postmenopausal women involved in this study. The participants had at least one year's history of postmenopausal hypertension. Their ages ranged (40-50) years. Their body mass index ranged (30-36 Kg/m 2). They were divided into two equal groups (treatment and control). Nitric oxide levels and blood pressure were measured in both groups in the initial exa...

Quetiapine is an antipsychotic drug that belongs to the group of nonconventional agents. Mainly u... more Quetiapine is an antipsychotic drug that belongs to the group of nonconventional agents. Mainly used to treat schizophrenia, bipolar depressive disorder, and exacerbations of manic and depressive episodes of this condition. It is also used to prevent these episodes of exacerbation, beside its many off-label uses. Atypical antipsychotics treat negative symptoms of psychosis without causing extra sedation, and help schizophrenics to integrate into society and, in addition, to remove unwanted extrapyramidal symptoms that conventional agents are known to exert. Unfortunately, these agents, including quetiapine, have other drawbacks the most serious of which are those associated with the disease spectrum of metabolic syndrome and, furthermore, the many interactions quetiapine may be involved in with other drugs in cases of polypharmacy. This review gives an update on quetiapine and provides a guideline to psychiatric caregivers, and importantly, undergraduates of medicine and pharmacy students on clinical uses (both dedicated and off-label), pharmacology, pharmacopeia, and intoxication that might occur following its use, and how to treat such a condition.

Journal of Chemical Biology, 2009

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processe... more Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than ...