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

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages

Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epi-dermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheri-tance. The mutation profile attests to the impact of consanguinity in these families

Studies on Dissolution Enhancement of Prednisolone, a Poorly Water-Soluble Drug by Solid Dispersion Technique

Introduction: Prednisolone is a class II substance according to the Biopharmaceutics Classification System. It is a poorly water soluble agent. The aim of the present study was to improve dissolution rate of a poorly water-soluble drug, prednisolone, by a solid dispersion technique. Methods: Solid dispersion of prednisolone was prepared with PEG 6000 or different carbohydrates such as lactose and dextrin with various ratios of the drug to carrier i.e., 1:10, 1:20 and 1:40. Solid dispersions were prepared by coevaporation method. The evaluation of the properties of the dispersions was performed using dissolution studies, Fourier-transform infrared spectroscopy and x-ray powder diffractometery. Results: The results indicated that lactose is suitable carriers to enhance the in vitro dissolution rate of prednisolone. The data from the x-ray diffraction showed that the drug was still detectable in its solid state in all solid dispersions except solid dispersions prepared by dextrin as carrier. The results from infrared spectroscopy showed no well-defined drug–carrier interactions for coevaporates. Conclusion: Solid dispersion of a poorly water-soluble drug, prednisolone may alleviate the problems of delayed and inconsistent rate of dissolution of the drug

Multigene Next-Generation Sequencing Panel Identifies Pathogenic Variants in Patients with Unknown Subtype of Epidermolysis Bullosa: Subclassification with Prognostic Implications

Purpose: Epidermolysis bullosa (EB), the prototype of heritable blistering diseases, is caused by mutations in as many as 19 distinct genes. In this study, we evaluated the molecular basis of EB in 93 families, many of them of unknown subtype. Methods: A next generation sequencing panel covering 21 EB-related genes was developed, and mutation profiles, together with clinical features, were used to classify the patients into distinct clinical categories. Results: A total of 72 pathogenic or likely pathogenic variants in 68 families were identified in 11 of the EB-associated candidate genes, most of them (75%) being homozygous consistent with considerable consanguinity in the cohort. Approximately half of the mutations (48.6%) were previously unreported. Refined analysis of the types of mutations with addition of variants of unknown significance suspected of causing clinically consistent disease in several patients allowed subclassification of patients into different subcategories of EB in 76 of 91 families, with prognostic implications. A genetically challenging case with homozygous loss-of-function pathogenic mutations in two different EB-associated genes resulting in different subtypes was identified. In addition, secondary findings included identification of known pathogenic variants in DSP associated with arrhythmogenic right ventricular cardiomyopathy. Conclusion: Utilization of next generation sequencing panel of EB-associated genes allowed diagnostic subclassification in the neonates particularly in families of unknown subtype, with prognostication of the overall long-term outcome of the disease

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

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.

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

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

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