A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Epilepsy as a Rare Neurologic Manifestation of Oculodentodigitalis Dysplasia

How to Cite this Article: Barzegar M, Sayadnasiri M, Tabrizi A. Epilepsy as a Rare Neurologic Manifestation of Oculodentodigitalis Dysplasia. Iran J Child Neurol 2012; 6(3): 39-43.Oculodentodigitalis dysplasia (ODDD) is an extremely rare inherited disorderinvolving the development of the face, eyes, teeth and limbs. In addition,some patients develop neurological problems mostly a spastic paraparesisassociated with white matter abnormalities on magnetic resonance imaging.This report describes a patient with epilepsy, a rare neurologic manifestationof this syndrome.ReferencesJudisch GF, Martin-Casals A, Hanson JW, Olin WH.Oculodentodigital dysplasia. Four new reports and aliterature review. Arch Ophthalmol 1979 May;97(5):878-84.Paznekas WA, Boyadjiev SA, Shapiro RE, DanielsO, Wollnik B, Keegan CE, et al. Connexin 43(GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 2003 Feb;72(2):408-18.Parashari UC, Khanduri S, Bhadury S, Qayyum FA.Radiographic diagnosis of a rare case of oculodentodigital dysplasia. SA J Radiology 2011:134-6.van Es RJ, Wittebol-Post D, Beemer FA. Oculodentodigital dysplasia with mandibular retrognathism and absenceof syndactyly:a case report with a novel mutation in the connexin 43 gene. Int J Oral Maxillofac Surg 2007 Sep;36(9):858-60.Aminabadi NA, Ganji AT, Vafaei A, Pourkazemi M,Oskouei SG. Oculodentodigital dysplasia: disease spectrum in an eight-year-old boy, his parents and asibling. J Clin Pediatr Dent 2009 Summer;33(4):337-41.Loddenkemper T, Grote K, Evers S, Oelerich M, StogbauerF. Neurological manifestations of the oculodentodigital dysplasia syndrome. J Neurol 2002 May;249(5):584-95.Opjordsmoen S, Nyberg-Hansen R. Hereditary spasticparaplegia with neurogenic bladder disturbances and syndactylia. Acta Neurol Scand 1980 Jan;61(1):35-41.Farmer TW, Wingfield MS, Lynch SA, Vogel FS, HuletteC, Katchinoff B, et al. Ataxia, chorea, seizures, and dementia. Pathologic features of a newly defined familial disorder. Arch Neurol 1989 Jul;46(7):774-79.Gorlin RJ, Meskin LH, St Geme JW. Oculodentodigital dysplasia. J Pediatr 1963 Jul;63:69-75.Orphanet report Series.Prevalence of rare disease:Bibliographic data-November 2011-Number 1.http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalenceof rare disease by alphabetical list.pdf. 1st November2011.Jones C, Baldrighi C, Mills J, Bush P, Ezaki M, OishiS. Oculodentodigital dysplasia: ulnar-sided syndactyly and its associated disorders. J Hand Surg Am. 2011 Nov;36(11):1816-21.Gutmann DH, Zackai EH, Mc Donald-McGinn DM,Fischbeck KH, Kamholz J. Oculodentodigital dysplasia syndrome associated with abnormal cerebral white matter.Am J Med Genet 1991 Oct;41(1):18-20.Schrander-Stumpel CT, Franke CL. Central nervous system abnormalities in oculodentodigital dysplasia.Genet Couns 1996;7(3):233-5.14. Ginsberg LE, Jewett T, Grub R, Mclean WT.Oculodental digital dysplasia: neuroimaging in a kindred. Neuroradiology 1996 Jan;38(1):84-6.15. Amador C, Mathews AM, Del Carmen, Montoya M,Laughridge ME, Everman DB, Holden KR .Expanding the neurologic phenotype of oculodentodigital dysplasiain a 4-generation Hispanic family. J Child Neurol 2008 Aug;23(8):901-5.

Baclofen Induced Encephalopathy in a 6-Year-Old Boy with Advanced Renal Failure

How to Cite This Article: Malak M, Barzgar M. Baclofen Induced Encephalopathy in a 6-Year-Old boy with Advanced Renal Failure. Iran J Child Neurol. Spring 2015;9(2):61-63. AbstractBaclofen is a drug for many diseases for all ages, but it is hazardous in patients with renal failure. This article talks about a case of baclofen overdose in a child with renal failure.A 6-year-old boy admitted to the emergency department with a loss of consciousness, hypotonia, and areflexia following administration of 20 mg baclofen (1mg/kg/daily) in total dose for his voiding dysfunction. His laboratory tests showed advanced renal failure. After withholding the medication andsupportive therapy, he recovered completely after two days. After arousal, he complained of insomnia, strange sensations on the skin, intentional tremors, and ataxia. He left the hospital in good condition in three days.Renal function control before baclofen administration is mandatory especially in high-risk groups. A total dose of 1mg/kg lead to encephalopathy in children with advanced renal failure, with subtle persistent complaints persist are often overlooked for a while

Boussinesq Modelling of Waves and Currents in the Presence of Submerged Detached/Discontinuous Breakwaters

The effect of beach configurations with the main focus on the detached submerged breakwater on shoreline currents is investigated numerically. The Boussinesq equations are used to model the beach with a constant slope, continuous submerged breakwater, and discontinuous/detached submerged breakwater. Our numerical simulation results show that the transient rip currents are generated near the shoreline at the beach with constant slope while the continuous submerged breakwater structure creates a calm beach area along the shoreline. The presence of the gap in submerged breakwater changes the currents along the shoreline by generating rip currents with two pairs of vortices. One pair of vorticities, located around the gap, damage the breakwater by transmitting sediments along the breakwater foundation and eroding its surface. The second pair, created near the shoreline, erodes the shoreline due to sediment transportation and leads to a dangerous and unsafe situation for swimmers. The rip current creates five main critical areas with the maximum velocity towards the shoreline and offshore. The first set of three areas (numbered 1, 2, 3) has an approximately average velocity of 1-1.25 m/s towards the shoreline. One of these areas (numbered 2) is located close to the shoreline and the other two (numbered 1 and 3) are found to occur near the edge of the detached part of the breakwater. The second set of the two areas (numbered by 4 and 5) has the average velocity that is higher than 2.1 m/s towards the offshore and is located at the beginning part of the rip neck. An approximately linear relationship between the returning velocity and the gap length is observed. As the gap length decreases the location of the areas (numbered 4 and 5) gets closer to the center of the gap. Our simulations indicate that the return velocity towards the offshore increases at the gap center while the gap length decreases. Furthermore, the velocity profiles have a sharp jump for gap length that is approximately smaller than 80 m. Also, the return velocity at the gap center is related to the height of the breakwater. The breakwater that is higher (the breakwater height d = 4.2 m) damps wave energy more than shorter breakwater and the return velocity decreases for this structure. For smaller heights (d = 3.7 and 3.2) damping is nearly the same and the returning flow varies depending on the available space through the gap. Specifically, the return velocity for d = 3.7 is higher than that for d = 3.2. The numerical results presented herein suggest that aggressive rip currents are generated in the case of detached submerged breakwater beach configurations

Refractory Convulsive Status Epilepticus in Children: Etiology, Associated Risk Factors and Outcome

How to Cite This Article: Barzegar M, Mahdavi M, Zalegolab behbehani A, Tabrizi A. Refractory Convulsive Status Epilepticus in Children: Etiology, Associated Risk Factors and Outcome. Iran J Child Neurol. Autumn 2015;9(4): 24-31.AbstractObjectiveRefractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient’s convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity.This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome.Materials & MethodsPatients with SE hospitalized in Tabriz Children’s Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital.ResultsAmong 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients’ age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in thosewith SE (P=0.006).ConclusionEtiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage

Very Severe Spinal Muscular Atrophy (Type 0): A Report of Three Cases

ObjectiveWe describe three patients with very severe Spinal Muscular Atrophy (SMA) presented with reduced fetal movement in utero, profound hypotonia, severe weakness and respiratory insufficiency at birth. In all infants, electrodiagnostic studies were compatible with a neurogenic pattern. In genetic studies, all cases had homozygous deletions of exons 7 and 8 of Survival Motor Neuron (SMN) and exon 5 of Neuronal Apoptosis Inhibitory Protein (NAIP) gene. SMA should be considered in the differential diagnosis of reduced fetal movement and respiratory insufficiency at birth

Sciatic Nerve Injection Palsy in Children, Electrophysiologic Pattern and Outcome: A Case Series Study

How to Cite This Article: Toopchizadeh V, Barzegar M, Habibzadeh A. Sciatic Nerve Injection Palsy in Children, Electrophysiologic Pattern and Outcome: A Case Series Study. Iran J Child Neurol. Summer 2015;9(3):69-72.AbstractSciatic nerve injury is one of the frequent mononeuropathies in children thatoccurs due to different causes such as nerve compression, trauma and stretchduring surgery. Gluteal injection is an uncommon cause of sciatic injury indeveloped countries. Poor techniques and frequent injections are the commoncause of injection palsy. Proneal division of the sciatic nerve is more prone toinjury due to anatomic and structural characteristics. The diagnosis is based onelectrophysiological studies and the recovery rate is poor. In this study, in aperiod of 2 years between 2012 and 2013, we report seven children under 6 years old (three females and four males) with abnormal gait and foot pain following gluteal injection in pediatric electrodiagnostic center. Five children had proneal component and two with tibial component injuries. Five children were followed for one year and only one showed good recovery

Treatment of a Pigmented Hypertrophic Scar by Low-Level Laser Therapy (LLLT): a Case Report

A hypertrophic scar is defined as an excess healing response that is a dilemma for physicians. Several therapies are available: intralesional corticosteroids, topical treatments, cryotherapy, surgery, radiation, silicone gel dressing and laser therapy.Pulsed-dye, Nd-Yag and CO2 lasers have been used for treatment of keloids and hypertrophic scars but recurrence is common. Recently Low-Level Laser Therapy(aluminum-gallium-arsenide (AlGaAs) Diode 980nm, red light (Mustung, KLO4,Helium Neon 630 nm) and blue light LED lasers have been used for closure of wounds. The aim of this report is to show the effectiveness of these lasers for the treatment of a hypertrophic scar on the forearm of a 40 year-old woman due to burning by gas explosion

Morphological and Physicochemical Evaluation of Modafinil-Eudragit RS100 Nanoformulations Prepared by Electrospray Method

Introduction: Modafinil is a wake-promoting agent approved by FDA for the treatment of narcolepsy and shift work sleep disorder. Due to its insolubility in water, the drug exhibits low oral bioavailability. Studies have shown that formulating poorly-soluble drugs as nanoparticles can improve the drugs physicochemical properties. Electrospraying is an uncomplicated and cost-benefit method for preparing nanoparticles that can easily be scaled up. Methods and Results: Modafinil and Eudragit RS100 were co-dissolved in methanol and acetone (1:1) with the drug: polymer ratios of 1:5 and 1:10 at various total solution concentrations (10%, 15% and 20%). The solutions were injected through a capillary tube on a Teflon screen at a rate of 2 ml/h. A voltage of 20-25 kV was applied between the injection needle and the Teflon screen. The particle size and morphology of resultant nanoparticles and nanofibers were evaluated via scanning electron microspore (SEM). Thermal behavior and crystallinity of the samples were studied by differential scanning calorimeter (DSC) and Powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) was used to determine any possible interaction between the drug and the polymer. In vitro drug release profile was studied at a pH of 6.8 via USP apparatus II. SEM results suggested that solutions with lower concentration created nanoparticles (100-300 nm) while increasing the concentration resulted in formation of nanofibers (50-100 nm). DSC and PXRD analysis revealed that electrosprayed Modafinil was transferred from crystalline to amorphous state. FTIR results indicated that hydrogen bonds might have formed between the drug and polymer. Drug release profile revealed that electrospraying process modified drug release pattern. Some of the formulations managed to increase the release rate whereas other formulations resulted in slower release. Conclusions: Electrospraying is a suitable method for fabricating nanofibers and nanoparticles of Modafinil. The resultant nanoformulations show properties such as reduced size, decreased crystallinity and modified release rate, thus help Modafinil to have higher oral bioavailability

Preparation of Gliclazide Nanoparticles via Electrospraying Method and Evaluation of Their Physicochemical Properties

Introduction:  Gliclazide is a second-generation sulfonylurea used in the treatment of non-insulin dependent diabetes mellitus. Gliclazide is practically insoluble in water, therefore, researchers try to find techniques to improve its physicochemical properties. On the other hand, researches has shown that nanoparticles are effective in improving the physicochemical characteristics of poorly water-soluble drugs. There are many methods to prepare nanoparticles, among all, electrospraying as a one-step and cost-benefit technique can  be easily applied in industrial scale. Methods and Results:  Gliclazide and polymer (Eudragit RS100 or PEG6000) were co-dissolved in acetone with drug: polymer ratios of 1:5 and 1:10, so that the polymer solution concentrations were 10, 15 and 20% (w/v). Then these solutions were electosprayed. The particle size and morphology were evaluated using scanning electron microscopy (SEM). The physicochemical characteristics of nanofibers and nanoparticles were evaluated by DSC thermograms, FTIR spectroscopy and X-Ray crystallography. Drug release profiles were studied as well. The size of prepared nanofibers and nanobeads, ranged from 100 nm-500 nm. Based on the physicochemical characteristics, there was a transition from crystalline to amorphous state of Gliclazide. No interaction between drug and polymers were observed in the prepared nanoparticles. In vitro drug release studies revealed that the drug-release patterns were improved in the prepared nanoparticles. Conclusions:  Electrospraying is a simple and low-cost method that can be used to produce Gliclazide nanoparticles in industrial scale and improve physicochemical properties of the drug