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BMC Complementary Medicine and Therapies Oct 2022Diabetic wounds are one of the most important issues in diabetic patients. It seems that Juglans regia L. leaf with antioxidant and anti-inflammatory potentials can be...
BACKGROUND
Diabetic wounds are one of the most important issues in diabetic patients. It seems that Juglans regia L. leaf with antioxidant and anti-inflammatory potentials can be profitable for healing of diabetic wounds. The aim of present study was to investigate the topical administration of Juglans regia L. leaf extract in diabetic wound healing.
METHODS
Seventy-five diabetic male rats were randomly divided into 5 groups (n = 15), including: untreated (Control) group, Eucerin group, 2% Juglans regia L. ointment (JRL 2%) group, 5% Juglans regia L. ointment (JRL 5%) group, and Phenytoin group as a reference drug. Sampling was performed at days 7, 14, and 21 after surgery. Evaluation tests included stereology, immunohistochemistry, molecular, and biomechanical.
RESULTS
Our results showed that the wound closure rate, volumes of newly formed of epidermis and dermis, density of fibroblasts and blood vessels, collagen deposition, density of proliferation cells, expression levels of TGF-β and VEGF genes, and biomechanical characteristics were significantly higher in extract groups compared to control and eucerin groups, however, these changes were considerable in the JRL 5% group (P < 0.05). This is while that the density of neutrophils and expression levels of TNF-α and IL-1β genes in the extract groups, especially in the JRL 5% group, were significantly reduced compared to control and eucerin groups (P < 0.05).
CONCLUSION
Topical administration of Juglans regia L. leaf extract, especially in 5% concentration, considerably accelerates diabetic wound healing.
Topics: Administration, Topical; Animals; Antioxidants; Collagen; Diabetes Mellitus; Juglans; Male; Ointments; Phenytoin; Plant Extracts; Rats; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Wound Healing
PubMed: 36192711
DOI: 10.1186/s12906-022-03735-6 -
Frontiers in Pharmacology 2023Captisol-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium. We aim to compare the intravenous and...
Comparison of pharmacokinetics and safety between CE-fosphenytoin sodium, fosphenytoin sodium, and phenytoin sodium after intravenous and intramuscular administration in healthy volunteers.
Captisol-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium. We aim to compare the intravenous and intramuscular bioavailability and safety between CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx), and phenytoin sodium (intravenous injection only). In pivotal study 1, 54 subjects were divided into three sequence groups that receive intravenous injection of 250 mg of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin sodium (R1) and 250 mg of phenytoin sodium (R2) in period 1. After a 14-day washout period, 36 subjects were randomized to two treatment sequence groups (T-R1 or R1-T, = 18 per group) in period 2, in which the subjects who received R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), while those who previously received R1 used T (R1-T). In pivotal study 2, a single intramuscular dose of T (400 mg PE) or R1 (400 mg PE) was administered according to the individual sequential treatment assignment in each period. There was a washout (14 days) period before receiving the next period study drug. T and R1 have similar pharmacokinetic characteristics regarding total and free phenytoin, showing bioequivalence of both drugs in the intravenous and intramuscular administration. The geometric mean ratio was close to 1 (0.98-1.06). The AUC of total and free phenytoin in subjects who intravenously received T and R1 was very similar to those who received R2, although their C was lower than that of the subjects who received R2. Overall, treatment with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular (i.m.) treatment, the incidence of drug-related AEs using T was similar to that using R1. Treatment with T and R1 had clearly superior tolerability than that with R2. CE-fosphenytoin sodium is a promising substitute for fosphenytoin sodium. http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).
PubMed: 38044946
DOI: 10.3389/fphar.2023.1204075 -
Yakugaku Zasshi : Journal of the... 2023Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined...
Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R were co-administered, the time to maximum plasma concentration (T) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.
Topics: Rats; Animals; Phenytoin; Enteral Nutrition; Administration, Oral; Dietary Fiber; Milk Proteins
PubMed: 36596543
DOI: 10.1248/yakushi.22-00162 -
Indian Journal of Dermatology,... 2016
Topics: Anticonvulsants; Edema; Female; Follow-Up Studies; Hand; Humans; Hyperpigmentation; Infusions, Intravenous; Kidney Transplantation; Middle Aged; Phenytoin; Risk Assessment; Seizures; Syndrome
PubMed: 26728832
DOI: 10.4103/0378-6323.172908 -
Indian Journal of Dermatology 2015Cutaneous pseudolymphomas are benign lymphoproliferative processes mimicking lymphomas clinically and histologically. One of the precipitating factors for pseudolymphoma...
Cutaneous pseudolymphomas are benign lymphoproliferative processes mimicking lymphomas clinically and histologically. One of the precipitating factors for pseudolymphoma is drugs like anticonvulsants, antidepressants and angiotensin-converting enzyme inhibitors. According to existing literature phenytoin-induced cutaneous pseudolymphomas are usually T-cell predominant. Most often withdrawal of the drug with or without short-course systemic steroids can attain a cure. Rarely malignant transformation has been reported years later despite withdrawal of the offending drug, which necessitates a long-term follow up of the affected. We report an 80-year-old male patient who was receiving phenytoin sodium and who presented with diffuse erythema and infiltrated skin lesions which histologically resembled cutaneous B-cell lymphoma. Substituting phenytoin with levetiracetam achieved resolution of symptoms. Further evaluation was suggestive of a reactive process. A detailed drug history is of paramount importance in differentiating drug-induced pseudolymphoma from lymphoma. Searching literature we could not find any previous reports of phenytoin-induced cutaneous B-cell pseudolymphoma.
PubMed: 26538730
DOI: 10.4103/0019-5154.164437 -
Epilepsia Apr 2024The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric...
OBJECTIVE
The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group.
METHODS
A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness.
RESULTS
Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (d = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (d = .47), crus I/II (d = .39), VIIIA (d = .45), and VIIIB (d = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls.
SIGNIFICANCE
We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.
Topics: Adult; Humans; Epilepsy, Temporal Lobe; Phenytoin; Cross-Sectional Studies; Epileptic Syndromes; Cerebellum; Seizures; Magnetic Resonance Imaging; Atrophy
PubMed: 38411286
DOI: 10.1111/epi.17881 -
Epilepsia May 2015To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the...
OBJECTIVES
To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.
METHODS
We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.
RESULTS
Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment.
SIGNIFICANCE
Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.
Topics: Anticonvulsants; Child; Child, Preschool; Cognition Disorders; Electroencephalography; Epilepsy; Female; Humans; Infant; KCNQ2 Potassium Channel; Male; Movement Disorders; Mutation; Neuroimaging; Pharmacogenetics; Retrospective Studies
PubMed: 25880994
DOI: 10.1111/epi.12984 -
Indian Journal of Pharmacology 2020The present study aimed to determine the pattern of prescription of antiepileptic drugs (AEDs) in a cohort of patients with epilepsy (PWE) attending a tertiary care...
OBJECTIVES
The present study aimed to determine the pattern of prescription of antiepileptic drugs (AEDs) in a cohort of patients with epilepsy (PWE) attending a tertiary care center of North India.
MATERIALS AND METHODS
Demographic variables including age, gender, age at onset, type and frequency of seizures, and prescription of all AEDs (dose and duration) were noted. Descriptive analysis of the use of AEDs was done, and their different combinations were studied.
RESULTS
A total of 1187 prescriptions were evaluated. Demography showed 65.7% of males; mean age of 21.9 years (range: 2-77 years), generalized seizures (53%), and focal seizures (47%). Only 21.8% of the patients were seizure free with no seizure in 1 year of treatment. The five most frequently prescribed AEDs out of 12 AEDs were sodium valproate (VPA) (49.6%), clobazam (CLB) (39.3%), levetiracetam (LEV) (28.4%), carbamazepine (CBZ) (27.3%), and phenytoin (PHT) (26.5%). Monotherapy was effective in 36.6% of the patients. Sodium VPA (39.4%), PHT (25.6%), and CBZ (20.1%) were commonly used as monotherapy. Polytherapy was required in 63.4% of the patients, and most commonly prescribed combinations were PHT + CLB (n = 53), sodium VPA + CLB (n = 62), CBZ + CLB (n = 45), PHT + sodium VPA + CLB (n = 28), and CBZ + sodium VPA + CLB (n = 31).
CONCLUSIONS
Polytherapy is a very common practice in our tertiary care center. Sodium VPA, a highly prescribed AED, results in good control of generalized seizures, whereas focal seizures are well controlled by CBZ alone as well as in combination. The present study highlights the commonly prescribed combinations of AEDs resulting in control of different types of seizures.
Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Female; Humans; India; Male; Middle Aged; Practice Patterns, Physicians'; Tertiary Care Centers; Young Adult
PubMed: 33078729
DOI: 10.4103/ijp.IJP_507_17 -
Frontiers in Pharmacology 2021The interest in AMPA receptors as a target for epilepsy treatment increased substantially after the approval of perampanel, a negative AMPA receptor allosteric...
The interest in AMPA receptors as a target for epilepsy treatment increased substantially after the approval of perampanel, a negative AMPA receptor allosteric antagonist, for the treatment of partial-onset seizures and generalized tonic-clonic seizures. Here we performed a screening for activity against native calcium-permeable AMPA receptors (CP-AMPARs) and calcium-impermeable AMPA receptors (CI-AMPARs) among different anticonvulsants using the whole-cell patch-clamp method on isolated Wistar rat brain neurons. Lamotrigine, topiramate, levetiracetam, felbamate, carbamazepine, tiagabin, vigabatrin, zonisamide, and gabapentin in 100-µM concentration were practically inactive against both major subtypes of AMPARs, while phenytoin reversibly inhibited them with IC50 of 30 ± 4 μM and 250 ± 60 µM for CI-AMPARs and CP-AMPARs, respectively. The action of phenytoin on CI-AMPARs was attenuated in experiments with high agonist concentrations, in the presence of cyclothiazide and at pH 9.0. Features of phenytoin action matched those of the CI-AMPARs pore blocker pentobarbital, being different from classical competitive inhibitors, negative allosteric inhibitors, and CP-AMPARs selective channel blockers. Close 3D similarity between phenytoin and pentobarbital also suggests a common binding site in the pore and mechanism of inhibition. The main target for phenytoin in the brain, which is believed to underlie its anticonvulsant properties, are voltage-gated sodium channels. Here we have shown for the first time that phenytoin inhibits CI-AMPARs with similar potency. Thus, AMPAR inhibition by phenytoin may contribute to its anticonvulsant properties as well as its side effects.
PubMed: 34950035
DOI: 10.3389/fphar.2021.775040 -
The Turkish Journal of Pediatrics 2023This study evaluated the efficacy of a single dose of phenytoin/fosphenytoin (PHT) to control repetitive seizures in children with benign convulsions with mild...
BACKGROUND
This study evaluated the efficacy of a single dose of phenytoin/fosphenytoin (PHT) to control repetitive seizures in children with benign convulsions with mild gastroenteritis (CwG).
METHODS
Children aged between 3 months and 5 years with CwG were retrospectively enrolled. Convulsions with mild gastroenteritis were defined as (a) seizures with acute gastroenteritis without fever or dehydration; (b) normal blood laboratory results; and (c) normal electroencephalography and brain imaging findings. Patients were divided into two groups according to whether or not intravenous PHT (10 mg/kg of phenytoin or phenytoin equivalents) was administered. Clinical manifestations and treatment efficacy were evaluated and compared.
RESULTS
Ten of 41 children eligible for inclusion received PHT. Compared to children in the non-PHT group, those in the PHT group had a higher number of seizures (5.2 ± 2.3 vs. 1.6 ± 1.0, P < 0.001) and a lower serum sodium level (133.5 ± 3.2 mmol/L vs. 137.2 ± 2.6 mmol/L, P = 0.001). Initial serum sodium levels were negatively correlated with seizure frequency (r = -0.438, P = 0.004). In all patients, seizures were completely resolved with a single dose of PHT. There were no significant adverse effects from PHT.
CONCLUSIONS
A single dose of PHT can effectively treat CwG with repetitive seizures. The serum sodium channel may play a role in seizure severity.
Topics: Child; Humans; Infant; Phenytoin; Retrospective Studies; Seizures; Gastroenteritis; Sodium
PubMed: 36866990
DOI: 10.24953/turkjped.2021.4574