Dexamethasone is classified as a corticosteroid and is commonly used among cancer patients to decrease the amount of swelling around the tumor. Among patients with cancer, in particular brain tumors, seizures can beco...Dexamethasone is classified as a corticosteroid and is commonly used among cancer patients to decrease the amount of swelling around the tumor. Among patients with cancer, in particular brain tumors, seizures can become a daily routine in their everyday lives. To counteract the seizures, an antiepileptic drug such as phenytoin is administered to act as an anticonvulsant. Phenytoin and dexamethasone are frequently administrated concurrently to brain cancer patients. A previous study has shown that phenytoin serum concentration decreases when administrated concurrently with dexamethasone. Thus, it is important to monitor the concentration of these two drugs in biological samples to ensure that the proper dosages are administrated to the patients. This study aims to develop an effective extraction and detection method for dexamethasone and phenytoin. A reverse-phase high-performance liquid chromatography (HPLC) method with UV/Vis detection has been developed to separate phenytoin and dexamethasone at 219 nm and 241 nm respectively from urine samples. The mobile phase consists of a mixture of 0.01 M KH2PO4, acetonitrile, and methanol adjusted to pH 5.6 (48:32:20) and is pumped at a flow rate of 1.0 mL/min. Calibration curves were prepared for phenytoin and dexamethasone (r2 > 0.99). An efficient solid-phase extraction (SPE) method for the extraction of dexamethasone and phenytoin from urine samples was developed with the use of C-18 cartridges. The percent recovery for phenytoin and dexamethasone is 95.4% (RSD = 1.15%) and 81.1% (RSD = 3.56%) respectively.展开更多
The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic dr...The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hippocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Functionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.展开更多
Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-g...Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/kg) or celecoxib (20 mg/kg), either alone or combined with phenytoin (50 mg/kg). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. Phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Linked Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: Phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptake of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.展开更多
Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies...Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.展开更多
Homogeneous liposome immunoassay for the determination of phenytoin was studied.Liposomes were prepared from cholesterol (CH) and phospholipids including dipalmitoyl phosphatidyl ethanolamine (DPPE) tbr conjugation wi...Homogeneous liposome immunoassay for the determination of phenytoin was studied.Liposomes were prepared from cholesterol (CH) and phospholipids including dipalmitoyl phosphatidyl ethanolamine (DPPE) tbr conjugation with thiol-containing antibodies. Hemin chloride was entrapped in the liposome and antibody was modified by reaction with 3' (2-pyndyl-dithio) propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. Antibody-coupled liposomes (immunoliposomes) were incubated with phenytoin and complement, and then with hemin substrate. The amount of hemin released from immunoliposomes, which increases with concentration increase of phenytoin, can be detected rapidly by determining the fluorescence with its substrate p-hydroxyphenyl propionic acid (HPPA)and hydrogen peroxide.展开更多
Phenytoin(5,5-diphenylhydantoin;DPH) induces expression of cytochromes P450(CYPs). Interactions between DPH and tacrolimus suggested that the persistence of CYP induction after discontinuation of DPH is dependent on t...Phenytoin(5,5-diphenylhydantoin;DPH) induces expression of cytochromes P450(CYPs). Interactions between DPH and tacrolimus suggested that the persistence of CYP induction after discontinuation of DPH is dependent on the history of administration and dosing period of DPH. However, the relationship between the duration of DPH administration and expression of CYPs in the liver and small intestine of rats is not known. Alterations in levels of P-glycoprotein(P-gp;MDR1;ABCB1) as well as CYPs cause drug interactions in the small intestine. We examined the effects of the duration of DPH administration on expression of CYPs and P-gp in the liver and small intestine of rats. Rats were treated with DPH(100 mg/kg,peroral(p.o.) twice a day(b.d.)) for 2, 4, 8, and 16 d. mRNA levels of CYPs and P-gp were examined using the total RNA extracted from the liver and duodenum 2 h and 24 h after the final administration of DPH. CYP3 A activities were determined using microsomes. DPH administration for 2 d and 4 d markedly increased m RNA levels of CYPs such as CYP3 A1, CYP3 A2,CYP2 B1, and CYP2 B2 in the liver. A relatively long duration of DPH administration(8 d and16 d) resulted in abolition of the induction of hepatic CYP but increased CYP3 A activities were maintained. These results suggest that the duration of DPH administration could be an important determinant of hepatic CYP induction.展开更多
Case 1: Mr. Li, a 55-year farmer from Hebeiprovince, paid his first visit on August 11, 1995. Thepatient complained of a sudden pain in the area fromhis left buttock down to the posterolateral aspect ofthe leg.
Background:The mechanism concerning gingival overgrowth as a side effect of phenytoin, a therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by measuring the intracellular calcium concentration...Background:The mechanism concerning gingival overgrowth as a side effect of phenytoin, a therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by measuring the intracellular calcium concentration ([Ca2+]i) of the gingival fibroblasts, it has been advocated that there is relationship between gingival overgrowth and phenytoin-induced alterations in the [Ca2+]i in gingival fibroblasts. To confirm that phenytoin elevates the [Ca2+]i, and if so, to find out its mode of action. Methods: The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Cells were soaked in a flexiperm chamber and perfused by a saline. Drugs at appropriate concentrations were added to the perfusate. Results: Phenytoin concentration-dependently elevated the [Ca2+]i. NPS2390, a calcium-sensing receptor (CaSR) blocker, significantly suppressed the phenytoin-induced [Ca2+]i elevation. U73122, a phospholipase C (PLC) inhibitor, inihibited the phenytoin-induced [Ca2+]i elevation. TMB-8, a blocker of inositol triphophate (IP3) receptors in ER, significantly depressed the phenytoin-induced [Ca2+]i elevation. m-3M3FBS, a PLC activator, enhanced the phenytoin-induced [Ca2+]i elevation. From the findings obtained, it is discussed as follows: The Ca2+-free saline and NPS2390, a CaSR antagonist, inhibited the phenytoin-induced [Ca2+]i rise;These results indicate that CaSRs exist in gingival fibroblasts and that CaSRs are involved in the phenytoin-induced [Ca2+]i rise;U73122 and TMB-8 depressed the phenytoin-induced [Ca2+]i elevation and furthermore, m-3M3FBS enhanced the phenytoin-induced [Ca2+]i elevation, showing that the Ca2+ release from the ER is involved in the phenytoin-induced [Ca2+]i elevation. Conclusion: We have concluded that phenytoin elevates the [Ca2+]i by activating CaSRs and enhancing the Ca2+ release from the Ca2+ stores in gingival fibroblasts.展开更多
Background: Gingival Overgrowth (GO) is a well documented and unwanted side effect that occurs mainly as a result of certain antiseizure, phenytoin. The aim of this study was to compare the effect of phenytoin on prol...Background: Gingival Overgrowth (GO) is a well documented and unwanted side effect that occurs mainly as a result of certain antiseizure, phenytoin. The aim of this study was to compare the effect of phenytoin on proliferation and production of IL1β and PGE2 in cultured human gingival fibroblasts (HGF) of children and adults. Materials and Methods: Normal HGFs were obtained from 4 healthy children and 4 adult and then were cultured with phenytoin (20 mg/ml). MTT test was used to evaluate the proliferation and ELISA to determine the level of IL1β and PGE2 production by HGFs. Analysis of proliferation were assessed by Independent T-Test and ANOVA analysis was used to assess the level of IL1β and PGE2 production with an a error level less than 0.05. Results: The proliferation of HGF was not affected significantly by phenytoin in both cultured fibroblast sources (P > 0.05). Phenytoin induced a significantly higher formation of IL1β and PGE2 in child’s HGFs as compared to adult’s HGFs (P < 0.05). Conclusion: The results suggest that different inflammatory responses and cytokine formation by child’s and adult’s HGFs are the probable key elements that cause different reactions of phenytoin therapy. More advanced and systematic studies are needed to verify these findings.展开更多
<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related dea...<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.</span>展开更多
文摘Dexamethasone is classified as a corticosteroid and is commonly used among cancer patients to decrease the amount of swelling around the tumor. Among patients with cancer, in particular brain tumors, seizures can become a daily routine in their everyday lives. To counteract the seizures, an antiepileptic drug such as phenytoin is administered to act as an anticonvulsant. Phenytoin and dexamethasone are frequently administrated concurrently to brain cancer patients. A previous study has shown that phenytoin serum concentration decreases when administrated concurrently with dexamethasone. Thus, it is important to monitor the concentration of these two drugs in biological samples to ensure that the proper dosages are administrated to the patients. This study aims to develop an effective extraction and detection method for dexamethasone and phenytoin. A reverse-phase high-performance liquid chromatography (HPLC) method with UV/Vis detection has been developed to separate phenytoin and dexamethasone at 219 nm and 241 nm respectively from urine samples. The mobile phase consists of a mixture of 0.01 M KH2PO4, acetonitrile, and methanol adjusted to pH 5.6 (48:32:20) and is pumped at a flow rate of 1.0 mL/min. Calibration curves were prepared for phenytoin and dexamethasone (r2 > 0.99). An efficient solid-phase extraction (SPE) method for the extraction of dexamethasone and phenytoin from urine samples was developed with the use of C-18 cartridges. The percent recovery for phenytoin and dexamethasone is 95.4% (RSD = 1.15%) and 81.1% (RSD = 3.56%) respectively.
基金supported in part by grants from the National Natural Science Foundation of China(Grant Nos.:81973405,82122071,and 82030111)to Dan XuHui Wang,the National Key R&D Program of China(Grant No.:2020YFA0803900)to Hui Wangthe Hubei Provincial Natural Science Foundation Outstanding Youth Found,China(Grant No.:2022CFA083).
文摘The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hippocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Functionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.
文摘Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/kg) or celecoxib (20 mg/kg), either alone or combined with phenytoin (50 mg/kg). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. Phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Linked Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: Phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptake of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.
文摘Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.
文摘Homogeneous liposome immunoassay for the determination of phenytoin was studied.Liposomes were prepared from cholesterol (CH) and phospholipids including dipalmitoyl phosphatidyl ethanolamine (DPPE) tbr conjugation with thiol-containing antibodies. Hemin chloride was entrapped in the liposome and antibody was modified by reaction with 3' (2-pyndyl-dithio) propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. Antibody-coupled liposomes (immunoliposomes) were incubated with phenytoin and complement, and then with hemin substrate. The amount of hemin released from immunoliposomes, which increases with concentration increase of phenytoin, can be detected rapidly by determining the fluorescence with its substrate p-hydroxyphenyl propionic acid (HPPA)and hydrogen peroxide.
文摘Phenytoin(5,5-diphenylhydantoin;DPH) induces expression of cytochromes P450(CYPs). Interactions between DPH and tacrolimus suggested that the persistence of CYP induction after discontinuation of DPH is dependent on the history of administration and dosing period of DPH. However, the relationship between the duration of DPH administration and expression of CYPs in the liver and small intestine of rats is not known. Alterations in levels of P-glycoprotein(P-gp;MDR1;ABCB1) as well as CYPs cause drug interactions in the small intestine. We examined the effects of the duration of DPH administration on expression of CYPs and P-gp in the liver and small intestine of rats. Rats were treated with DPH(100 mg/kg,peroral(p.o.) twice a day(b.d.)) for 2, 4, 8, and 16 d. mRNA levels of CYPs and P-gp were examined using the total RNA extracted from the liver and duodenum 2 h and 24 h after the final administration of DPH. CYP3 A activities were determined using microsomes. DPH administration for 2 d and 4 d markedly increased m RNA levels of CYPs such as CYP3 A1, CYP3 A2,CYP2 B1, and CYP2 B2 in the liver. A relatively long duration of DPH administration(8 d and16 d) resulted in abolition of the induction of hepatic CYP but increased CYP3 A activities were maintained. These results suggest that the duration of DPH administration could be an important determinant of hepatic CYP induction.
文摘Case 1: Mr. Li, a 55-year farmer from Hebeiprovince, paid his first visit on August 11, 1995. Thepatient complained of a sudden pain in the area fromhis left buttock down to the posterolateral aspect ofthe leg.
文摘Background:The mechanism concerning gingival overgrowth as a side effect of phenytoin, a therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by measuring the intracellular calcium concentration ([Ca2+]i) of the gingival fibroblasts, it has been advocated that there is relationship between gingival overgrowth and phenytoin-induced alterations in the [Ca2+]i in gingival fibroblasts. To confirm that phenytoin elevates the [Ca2+]i, and if so, to find out its mode of action. Methods: The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Cells were soaked in a flexiperm chamber and perfused by a saline. Drugs at appropriate concentrations were added to the perfusate. Results: Phenytoin concentration-dependently elevated the [Ca2+]i. NPS2390, a calcium-sensing receptor (CaSR) blocker, significantly suppressed the phenytoin-induced [Ca2+]i elevation. U73122, a phospholipase C (PLC) inhibitor, inihibited the phenytoin-induced [Ca2+]i elevation. TMB-8, a blocker of inositol triphophate (IP3) receptors in ER, significantly depressed the phenytoin-induced [Ca2+]i elevation. m-3M3FBS, a PLC activator, enhanced the phenytoin-induced [Ca2+]i elevation. From the findings obtained, it is discussed as follows: The Ca2+-free saline and NPS2390, a CaSR antagonist, inhibited the phenytoin-induced [Ca2+]i rise;These results indicate that CaSRs exist in gingival fibroblasts and that CaSRs are involved in the phenytoin-induced [Ca2+]i rise;U73122 and TMB-8 depressed the phenytoin-induced [Ca2+]i elevation and furthermore, m-3M3FBS enhanced the phenytoin-induced [Ca2+]i elevation, showing that the Ca2+ release from the ER is involved in the phenytoin-induced [Ca2+]i elevation. Conclusion: We have concluded that phenytoin elevates the [Ca2+]i by activating CaSRs and enhancing the Ca2+ release from the Ca2+ stores in gingival fibroblasts.
文摘Background: Gingival Overgrowth (GO) is a well documented and unwanted side effect that occurs mainly as a result of certain antiseizure, phenytoin. The aim of this study was to compare the effect of phenytoin on proliferation and production of IL1β and PGE2 in cultured human gingival fibroblasts (HGF) of children and adults. Materials and Methods: Normal HGFs were obtained from 4 healthy children and 4 adult and then were cultured with phenytoin (20 mg/ml). MTT test was used to evaluate the proliferation and ELISA to determine the level of IL1β and PGE2 production by HGFs. Analysis of proliferation were assessed by Independent T-Test and ANOVA analysis was used to assess the level of IL1β and PGE2 production with an a error level less than 0.05. Results: The proliferation of HGF was not affected significantly by phenytoin in both cultured fibroblast sources (P > 0.05). Phenytoin induced a significantly higher formation of IL1β and PGE2 in child’s HGFs as compared to adult’s HGFs (P < 0.05). Conclusion: The results suggest that different inflammatory responses and cytokine formation by child’s and adult’s HGFs are the probable key elements that cause different reactions of phenytoin therapy. More advanced and systematic studies are needed to verify these findings.
文摘<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.</span>
