Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) prot... more Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) protocol has been introduced as a rodent model of depression combining the roles of immune activation and chronic psychological stress. However, the impact of this paradigm on cognitive functioning has not been investigated hitherto. METHODS This study evaluated LPS/CMS-induced cognitive effects and the role of glycogen synthase kinase-3β (GSK-3β) activation with subsequent neuroinflammation and pathological tau deposition in the pathogenesis of these effects using lithium (Li) as a tool for GSK-3 inhibition. RESULTS LPS pre-challenge reduced CMS-induced neuroinflammation, depressive-like behavior and cognitive inflexibility. It also improved spatial learning but increased GSK-3β expression and exaggerated hyperphosphorylated tau accumulation in hippocampus and prefrontal cortex. Li ameliorated CMS and LPS/CMS-induced depressive and cognitive deficits, reduced GSK-3β over-expression and tau hyperphosphorylation, impeded neuroinflammation and enhanced neuronal survival. CONCLUSION This study draws attention to LPS/CMS-triggered cognitive changes and highlights how prior low-dose immune challenge could develop an adaptive capacity to buffer inflammatory damage and maintain the cognitive abilities necessary to withstand threats. This work also underscores the favorable effect of Li (as a GSK-3β inhibitor) in impeding exaggerated tauopathy and neuroinflammation, rescuing neuronal survival and preserving cognitive functions. Yet, further in-depth studies utilizing different low-dose LPS challenge schedules are needed to elucidate the complex interactions between immune activation and chronic stress exposure.
Background: Recent evidence links the pathophysiology of asthma to cardiovascular diseases. A pro... more Background: Recent evidence links the pathophysiology of asthma to cardiovascular diseases. A proatherogenic role of leukotrienes has been reported which is suggestive of a potential anti-atherosclerotic effect for leukotriene antagonists. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by altering systemic inflammation. Aim: the present study was designed to investigate the impact of the leukotriene antagonist montelukast on vascular dysfunctions in guinea pigs exposed to chronic ovalbumin (OVA) challenge and fed high fat diet (HFD). The potential anti-atherosclerotic effects of montelukast were compared to those of the inhaled corticosteroid fluticasone. Method: Forty-eight male guinea pigs were divided into: control non-asthmatic-chow fed (n=6), non-asthmatic-dyslipidemic; fed HFD (n=6), asthmatic-chow fed (n=18), and asthmatic-dyslipidemic groups (n=18), the last 2 groups were further subdivided into 3 groups (n=6 each): vehi...
Background: depression may be considered "the disease of the modern era". With a high p... more Background: depression may be considered "the disease of the modern era". With a high prevalence worldwide causing significant morbidity and mortality and constituting a heavy burden on social and economic welfare. Despite decades-long research the exact pathogenesis of depression is still not fully understood. Aims: to investigate the behvioral deficits elicited by exposure to the combined model of lipopolysaccharide (LPS) then chronic mild stress (CMS) in male Wistar rats and to investigate the putative role of inflammatory cytokine production induced lipopolysaccharide exposure together with chronic stress in the pathogenesis of depressive like behaviour. Materials and Methods: Sixty five Male Wistar rats were divided into two groups; Control group (n=29): naive rats left undisturbed, not exposed to stress and LPS/CMS exposed group (n=27). Results: exposure to LPS/CMS model induced a depressive-like behavior manifested by a decline in body weight gain, alongside an incr...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2020
Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency ... more Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted. Although strong evidences support the valproic acid (VPA) model of autism, yet a controversy exists regarding the best timing of exposure whether prenatal or postnatal. Accordingly, this study was designed to compare the time dependent effects of VPA exposure as regard its ability to induce autistic like changes in male Wistar rats. In this study, two different protocols of VPA exposure (prenatal and postnatal) were compared at different levels (behavioral, neurochemical and histopathological). Results of this study revealed that both prenatal and postnatal VPA exposures induced autistic-like behaviors manifested by reduced social interaction, increased repetitive stereotyped behavior and anxiety, cognitive dysfunction, lowered sensitivity to pain, and neurodevelopmental delay. Furthermore, inflammatory cytokines and oxidative/nitrosative stress markers were elevated in prefrontal cortex and hippocampal homogenates. Likewise, histopathological and immunohistochemical assessment confirmed the neurodegenerative and the apoptotic changes in prefrontal cortex, hippocampus and cerebellum exhibited by decreased viable cells number and Nissl's granules optical density, and increased caspase-3 immunoreactivity respectively. Interestingly, ASD core symptoms and histopathological changes were significantly (P < 0.05) altered in prenatal VPA model compared to postnatal VPA model. Additionally, postnatal mortality in prenatal model (4.3%) was much lower compared to the postnatal model (22.7%). In conclusion, our study overweighs the ability of prenatal VPA model over postnatal VPA model to induce behavioral and neuropathological alterations that simulate those observed in autistic individuals with a lower postnatal animal mortality, highlighting the privilege of prenatal over postnatal VPA exposure as a translational model for understanding pathophysiology and developing novel targets for management of ASD.
Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of mul... more Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/β-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and the effects of Lithium (Li) on the expression of this pathway as a method to identify a plausible link between exposure to chronic stress, microglial activation, and neuroinflammation. METHODS: The effect of chronic administration of Li was investigated on behavioral changes, hippocampal expression of Wnt-DVL-GSK3β-β-catenin signaling pathway, and microglial activation in CMS-exposed male Wistar rats RESULTS: CMS induced a depressive-like behavior associated with increased pro-inflammatory microglial activation and reduced hippocampal expression of the Wnt/β-catenin signaling pathway. Chronic Li treatment ameliorated stress induced-behavioral changes, reduced microglial activation and enhanced the hippocampal expression of Wnt/β-catenin signaling pathway. CONCLUSION: This work highlights that Li-induced inhibition of GSK-3β with subsequent accumulation of β-catenin could impede pro-inflammatory microglia activation which is a key pathological hallmark associated with depression. Wnt/β-catenin signaling represents a promising therapeutic target, not only for alleviation of depression, but also for a wide array of neurological disorders.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2019
Depression and cardiovascular disease (CVD) are two faces of one coin. A pro-inflammatory state w... more Depression and cardiovascular disease (CVD) are two faces of one coin. A pro-inflammatory state was previously suggested in the pathology of both diseases. We investigated the effect of chronic administration (2 weeks) of imipramine (20 mg/kg/day) and pentoxifylline (50 mg/kg/day) on behavioral, aortic histological abnormalities, and level of circulating endothelial progenitor cells (CEPCs) in peripheral blood of male Wistar rats exposed to chronic mild stress (CMS) and high-fat diet. Exposure to CMS and high-fat diet induced a depressive-like behavior alongside aortic immunohistochemical changes associated with an increase in aortic TNF-α level. Markers of CEPCs, VEGFR-2 and CD133, were significantly disturbed in aortic sections, as compared to control animals and those exposed to CMS while fed high-fat diet, although flowcytometric analysis did not show any significant changes in the level of CEPCs in peripheral blood. Chronic pentoxifylline treatment was more effective in ameliorating the histological changes and endothelial damage compared to imipramine. Pro-inflammatory cytokines-induced disturbances in CEPCs could constitute a plausible link between depression and atherosclerotic cardiovascular disease. Current antidepressants reduce symptoms of depression without tackling the underlying link between it and cardiovascular disease. Targeting pro-inflammatory cytokines might open a new therapeutic approach to alleviate depression and reduce the risk of mortality from cardiovascular disease.
Depression is the disease of the modern era. The lack of response to the available antidepressant... more Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS)...
Naunyn-Schmiedeberg's archives of pharmacology, Jan 29, 2018
Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its respon... more Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its response to antidepressants. This study aimed to determine the effect of metformin (MET) on the cognitive and antidepressant activity of fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive function, biochemical, and histopathological studies were performed in non-HFD- and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and lipid profile, reduced adiponectin level, brain-derived neurotrophic factor (BDNF) expression, and increased corticosterone and c-Jun. All these were aggravated by HFD. MET, FLU and their combination produced significant improvement in lipid profile with significant increase in adiponectin and BDNF expression. Corticosterone, body weight and insulin resistance showed significant decrease in the treated groups. Moreover, there was a significan...
Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway... more Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway may be involved in their relation. To evaluate the impact of depression on NASH through the involvement of JNK1 and to assess the effect of sitagliptin and metformin on hepatic JNK1 expression in both NASH and NASH associated with depression. Eight groups of male Wistar rats were used: naïve rats, non-stressed NASH, non-stressed NASH sitagliptin treated, non-stressed NASH metformin treated, stressed, stressed NASH untreated, stressed NASH sitagliptin treated and stressed NASH metformin treated. Behavioral, biochemical, molecular and histopathological studies were performed. Non-stressed NASH group showed depressive like symptoms, disturbed glucose homeostasis, impairment of liver functions, decrease adiponectin and increase malondialdehyde, which were aggreviated by stress. Sitagliptin produced significant improvement compared to metformin regarding biochemical and histopathological par...
Ceftriaxone is a commonly used antibiotic for various infections such as respiratory tract infect... more Ceftriaxone is a commonly used antibiotic for various infections such as respiratory tract infection, urinary tract infection, and enteric fever, as well as in surgical prophylaxis. Hypersensitivity reactions after ceftriaxone therapy are uncommon but are potentially life-threatening, and they may lead to cardiac arrest. Here we report a 44-year-old man who presented with bradycardia, bronchospasm, hypotension, and cardiac arrest (asystole) after a single injected dose of ceftriaxone introduced for surgical prophylaxis. Epinephrine was given intravenously, and cardiopulmonary resuscitation was performed successfully. The patient regained his conscious level 2 h later and became hemodynamically stable within 4 h; next, he was extubated and closely observed for 24 h and then discharged. Physicians should be aware of the risk of anaphylaxis and asystole that may occur after the first dose of ceftriaxone and be ready for managing it properly.
Phenytoin is a widely used anticonvulsant drug in the ICU that requires therapeutic drug monitori... more Phenytoin is a widely used anticonvulsant drug in the ICU that requires therapeutic drug monitoring. It carries a major risk of dose-related toxicity because of its saturation (zero-order) pharmacokinetic. Hepatic injury with phenytoin is common and varies from almost trivial to massive necrosis and is usually hepatocellular. Here, we report on a 45-year-old woman who was admitted to the ICU with subarachnoid hemorrhage and developed an acute liver injury 16 days after phenytoin injection. Phenytoin was stopped and replaced by oxcarbazepine. Possible drug interactions and risk factors are also discussed. Case presentation The present case is a 45-year-old woman who was admitted to the ICU on 26 July 2010 with subarachnoid hemorrhage and disturbed level of consciousness. On admission, lab investigations were as follows: Hb level, 10.5 g/dl; white blood cell count, 10 Â 10 3 /mm 3 ; platelet count, 233 Â 10 3 / mm 3 ; aspartate aminotransferase (AST) level, 64 IU/l; alanine aminotrans...
Surgical site infections account for B15% of nosocomial infections and are associated with prolon... more Surgical site infections account for B15% of nosocomial infections and are associated with prolonged hospital stay and increased costs. Prophylactic use of antibiotics aims at reducing the incidence of postsurgical wound infection. Inappropriate prophylaxis, whether unnecessary use of broad-spectrum agents or continuation of therapy beyond the recommended time period, is frequently seen. Indeed, this increases the risk of adverse effects and promotes the emergence of resistant organisms. Controversy remains as to the necessity of prophylaxis in specific surgical procedures, as well as with regard to the duration of prophylaxis. The aim of this review is to discuss the criteria upon which decisions pertaining to the use of prophylactic antibiotics are based using the best clinical evidence available. Special emphasis is directed towards the selection and proper time and duration of administration. This review focuses on gastroenterological surgeries. Analyses of other surgeries will ...
Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) prot... more Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) protocol has been introduced as a rodent model of depression combining the roles of immune activation and chronic psychological stress. However, the impact of this paradigm on cognitive functioning has not been investigated hitherto. METHODS This study evaluated LPS/CMS-induced cognitive effects and the role of glycogen synthase kinase-3β (GSK-3β) activation with subsequent neuroinflammation and pathological tau deposition in the pathogenesis of these effects using lithium (Li) as a tool for GSK-3 inhibition. RESULTS LPS pre-challenge reduced CMS-induced neuroinflammation, depressive-like behavior and cognitive inflexibility. It also improved spatial learning but increased GSK-3β expression and exaggerated hyperphosphorylated tau accumulation in hippocampus and prefrontal cortex. Li ameliorated CMS and LPS/CMS-induced depressive and cognitive deficits, reduced GSK-3β over-expression and tau hyperphosphorylation, impeded neuroinflammation and enhanced neuronal survival. CONCLUSION This study draws attention to LPS/CMS-triggered cognitive changes and highlights how prior low-dose immune challenge could develop an adaptive capacity to buffer inflammatory damage and maintain the cognitive abilities necessary to withstand threats. This work also underscores the favorable effect of Li (as a GSK-3β inhibitor) in impeding exaggerated tauopathy and neuroinflammation, rescuing neuronal survival and preserving cognitive functions. Yet, further in-depth studies utilizing different low-dose LPS challenge schedules are needed to elucidate the complex interactions between immune activation and chronic stress exposure.
Background: Recent evidence links the pathophysiology of asthma to cardiovascular diseases. A pro... more Background: Recent evidence links the pathophysiology of asthma to cardiovascular diseases. A proatherogenic role of leukotrienes has been reported which is suggestive of a potential anti-atherosclerotic effect for leukotriene antagonists. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by altering systemic inflammation. Aim: the present study was designed to investigate the impact of the leukotriene antagonist montelukast on vascular dysfunctions in guinea pigs exposed to chronic ovalbumin (OVA) challenge and fed high fat diet (HFD). The potential anti-atherosclerotic effects of montelukast were compared to those of the inhaled corticosteroid fluticasone. Method: Forty-eight male guinea pigs were divided into: control non-asthmatic-chow fed (n=6), non-asthmatic-dyslipidemic; fed HFD (n=6), asthmatic-chow fed (n=18), and asthmatic-dyslipidemic groups (n=18), the last 2 groups were further subdivided into 3 groups (n=6 each): vehi...
Background: depression may be considered "the disease of the modern era". With a high p... more Background: depression may be considered "the disease of the modern era". With a high prevalence worldwide causing significant morbidity and mortality and constituting a heavy burden on social and economic welfare. Despite decades-long research the exact pathogenesis of depression is still not fully understood. Aims: to investigate the behvioral deficits elicited by exposure to the combined model of lipopolysaccharide (LPS) then chronic mild stress (CMS) in male Wistar rats and to investigate the putative role of inflammatory cytokine production induced lipopolysaccharide exposure together with chronic stress in the pathogenesis of depressive like behaviour. Materials and Methods: Sixty five Male Wistar rats were divided into two groups; Control group (n=29): naive rats left undisturbed, not exposed to stress and LPS/CMS exposed group (n=27). Results: exposure to LPS/CMS model induced a depressive-like behavior manifested by a decline in body weight gain, alongside an incr...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2020
Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency ... more Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted. Although strong evidences support the valproic acid (VPA) model of autism, yet a controversy exists regarding the best timing of exposure whether prenatal or postnatal. Accordingly, this study was designed to compare the time dependent effects of VPA exposure as regard its ability to induce autistic like changes in male Wistar rats. In this study, two different protocols of VPA exposure (prenatal and postnatal) were compared at different levels (behavioral, neurochemical and histopathological). Results of this study revealed that both prenatal and postnatal VPA exposures induced autistic-like behaviors manifested by reduced social interaction, increased repetitive stereotyped behavior and anxiety, cognitive dysfunction, lowered sensitivity to pain, and neurodevelopmental delay. Furthermore, inflammatory cytokines and oxidative/nitrosative stress markers were elevated in prefrontal cortex and hippocampal homogenates. Likewise, histopathological and immunohistochemical assessment confirmed the neurodegenerative and the apoptotic changes in prefrontal cortex, hippocampus and cerebellum exhibited by decreased viable cells number and Nissl's granules optical density, and increased caspase-3 immunoreactivity respectively. Interestingly, ASD core symptoms and histopathological changes were significantly (P < 0.05) altered in prenatal VPA model compared to postnatal VPA model. Additionally, postnatal mortality in prenatal model (4.3%) was much lower compared to the postnatal model (22.7%). In conclusion, our study overweighs the ability of prenatal VPA model over postnatal VPA model to induce behavioral and neuropathological alterations that simulate those observed in autistic individuals with a lower postnatal animal mortality, highlighting the privilege of prenatal over postnatal VPA exposure as a translational model for understanding pathophysiology and developing novel targets for management of ASD.
Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of mul... more Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/β-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and the effects of Lithium (Li) on the expression of this pathway as a method to identify a plausible link between exposure to chronic stress, microglial activation, and neuroinflammation. METHODS: The effect of chronic administration of Li was investigated on behavioral changes, hippocampal expression of Wnt-DVL-GSK3β-β-catenin signaling pathway, and microglial activation in CMS-exposed male Wistar rats RESULTS: CMS induced a depressive-like behavior associated with increased pro-inflammatory microglial activation and reduced hippocampal expression of the Wnt/β-catenin signaling pathway. Chronic Li treatment ameliorated stress induced-behavioral changes, reduced microglial activation and enhanced the hippocampal expression of Wnt/β-catenin signaling pathway. CONCLUSION: This work highlights that Li-induced inhibition of GSK-3β with subsequent accumulation of β-catenin could impede pro-inflammatory microglia activation which is a key pathological hallmark associated with depression. Wnt/β-catenin signaling represents a promising therapeutic target, not only for alleviation of depression, but also for a wide array of neurological disorders.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2019
Depression and cardiovascular disease (CVD) are two faces of one coin. A pro-inflammatory state w... more Depression and cardiovascular disease (CVD) are two faces of one coin. A pro-inflammatory state was previously suggested in the pathology of both diseases. We investigated the effect of chronic administration (2 weeks) of imipramine (20 mg/kg/day) and pentoxifylline (50 mg/kg/day) on behavioral, aortic histological abnormalities, and level of circulating endothelial progenitor cells (CEPCs) in peripheral blood of male Wistar rats exposed to chronic mild stress (CMS) and high-fat diet. Exposure to CMS and high-fat diet induced a depressive-like behavior alongside aortic immunohistochemical changes associated with an increase in aortic TNF-α level. Markers of CEPCs, VEGFR-2 and CD133, were significantly disturbed in aortic sections, as compared to control animals and those exposed to CMS while fed high-fat diet, although flowcytometric analysis did not show any significant changes in the level of CEPCs in peripheral blood. Chronic pentoxifylline treatment was more effective in ameliorating the histological changes and endothelial damage compared to imipramine. Pro-inflammatory cytokines-induced disturbances in CEPCs could constitute a plausible link between depression and atherosclerotic cardiovascular disease. Current antidepressants reduce symptoms of depression without tackling the underlying link between it and cardiovascular disease. Targeting pro-inflammatory cytokines might open a new therapeutic approach to alleviate depression and reduce the risk of mortality from cardiovascular disease.
Depression is the disease of the modern era. The lack of response to the available antidepressant... more Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS)...
Naunyn-Schmiedeberg's archives of pharmacology, Jan 29, 2018
Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its respon... more Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its response to antidepressants. This study aimed to determine the effect of metformin (MET) on the cognitive and antidepressant activity of fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive function, biochemical, and histopathological studies were performed in non-HFD- and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and lipid profile, reduced adiponectin level, brain-derived neurotrophic factor (BDNF) expression, and increased corticosterone and c-Jun. All these were aggravated by HFD. MET, FLU and their combination produced significant improvement in lipid profile with significant increase in adiponectin and BDNF expression. Corticosterone, body weight and insulin resistance showed significant decrease in the treated groups. Moreover, there was a significan...
Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway... more Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway may be involved in their relation. To evaluate the impact of depression on NASH through the involvement of JNK1 and to assess the effect of sitagliptin and metformin on hepatic JNK1 expression in both NASH and NASH associated with depression. Eight groups of male Wistar rats were used: naïve rats, non-stressed NASH, non-stressed NASH sitagliptin treated, non-stressed NASH metformin treated, stressed, stressed NASH untreated, stressed NASH sitagliptin treated and stressed NASH metformin treated. Behavioral, biochemical, molecular and histopathological studies were performed. Non-stressed NASH group showed depressive like symptoms, disturbed glucose homeostasis, impairment of liver functions, decrease adiponectin and increase malondialdehyde, which were aggreviated by stress. Sitagliptin produced significant improvement compared to metformin regarding biochemical and histopathological par...
Ceftriaxone is a commonly used antibiotic for various infections such as respiratory tract infect... more Ceftriaxone is a commonly used antibiotic for various infections such as respiratory tract infection, urinary tract infection, and enteric fever, as well as in surgical prophylaxis. Hypersensitivity reactions after ceftriaxone therapy are uncommon but are potentially life-threatening, and they may lead to cardiac arrest. Here we report a 44-year-old man who presented with bradycardia, bronchospasm, hypotension, and cardiac arrest (asystole) after a single injected dose of ceftriaxone introduced for surgical prophylaxis. Epinephrine was given intravenously, and cardiopulmonary resuscitation was performed successfully. The patient regained his conscious level 2 h later and became hemodynamically stable within 4 h; next, he was extubated and closely observed for 24 h and then discharged. Physicians should be aware of the risk of anaphylaxis and asystole that may occur after the first dose of ceftriaxone and be ready for managing it properly.
Phenytoin is a widely used anticonvulsant drug in the ICU that requires therapeutic drug monitori... more Phenytoin is a widely used anticonvulsant drug in the ICU that requires therapeutic drug monitoring. It carries a major risk of dose-related toxicity because of its saturation (zero-order) pharmacokinetic. Hepatic injury with phenytoin is common and varies from almost trivial to massive necrosis and is usually hepatocellular. Here, we report on a 45-year-old woman who was admitted to the ICU with subarachnoid hemorrhage and developed an acute liver injury 16 days after phenytoin injection. Phenytoin was stopped and replaced by oxcarbazepine. Possible drug interactions and risk factors are also discussed. Case presentation The present case is a 45-year-old woman who was admitted to the ICU on 26 July 2010 with subarachnoid hemorrhage and disturbed level of consciousness. On admission, lab investigations were as follows: Hb level, 10.5 g/dl; white blood cell count, 10 Â 10 3 /mm 3 ; platelet count, 233 Â 10 3 / mm 3 ; aspartate aminotransferase (AST) level, 64 IU/l; alanine aminotrans...
Surgical site infections account for B15% of nosocomial infections and are associated with prolon... more Surgical site infections account for B15% of nosocomial infections and are associated with prolonged hospital stay and increased costs. Prophylactic use of antibiotics aims at reducing the incidence of postsurgical wound infection. Inappropriate prophylaxis, whether unnecessary use of broad-spectrum agents or continuation of therapy beyond the recommended time period, is frequently seen. Indeed, this increases the risk of adverse effects and promotes the emergence of resistant organisms. Controversy remains as to the necessity of prophylaxis in specific surgical procedures, as well as with regard to the duration of prophylaxis. The aim of this review is to discuss the criteria upon which decisions pertaining to the use of prophylactic antibiotics are based using the best clinical evidence available. Special emphasis is directed towards the selection and proper time and duration of administration. This review focuses on gastroenterological surgeries. Analyses of other surgeries will ...
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Papers by Sawsan Aboul-Fotouh