Role of ABCB1 C3435T variant in response to antiepileptic drugs in epilepsy: a review

Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area

Comparative analysis of transformed potato microtubers and its non-transformed counterpart using some biochemical analysis along with inter simple sequence repeat (ISSR) marker

The rapid progress of transgenic biotechnology has significantly promoted the development and production of genetically modified (GM) crops. The aim of this study was to compare some compositional analysis and genetic variation of transformed potato microtubers (Solanum tuberosum L. Desiree) line (which harbor potato virus Y coat protein gene) with its conventional line in order to understand the metabolic and genomic changes associated with the transformation process. The constituents measured were: amino acids profile, minerals content, reducing sugar, vitamin C, total phenolic, total flavonoid, β-carotene and antioxidant activity. Also, PCR based assay using inter simple sequence repeat (ISSR) was employed to characterize the genetic variation between both lines. The data demonstrated that, there were no significant differences between the transformed and nontransformed line in total amount of amino acids, some minerals, total phenolic, total flavonoid and β- carotene contents. Obtained results of the ISSR profile was efficiently discriminated in both selected lines at DNA level. Generally, it was concluded that the transformed microtubers line was confirmed to be similar to that of the non-transformed microtubers line.Key words: Amino acids, genetic modification, phenolic content, reducing sugar, Solanum tuberosum

MicroRNA Nanocarriers for the Treatment of Chronic Obstructive Pulmonary Disease

Chronic obstruction pulmonary disease (COPD) is a major cause of morbidity and mortality across the world. COPD is currently the fourth leading cause of death in the world and is predicted to become the third leading cause of chronic illness and death worldwide by 2030. There are several therapeutic strategies to reduce COPD symptoms and complications such as; bronchodilator medications, antibiotics, inhaled corticosteroids and rehabilitation. However, none of the available pharmacological or non-pharmacological treatments for COPD have been shown to delay or correct long-term defects in lung function. Small nucleic acids such as non-coding RNA (ncRNA) and interference microRNA (miRNA) have recently gained attention as a new class of therapeutics for various genetic diseases. Modulation of miRNA expression and function represents a promising strategy for therapeutic intervention in disorders such as inflammatory lung disease including COPD. In this study the aim was to design, formulate and characterise polymeric nanoparticles (NPs) containing miR-146a. This was followed by spray-dying using L-leucine and mannitol to prepare dry powder nanocomposite microparticles (NCMPs) for pulmonary delivery. Anionic and cationic poly (glycerol adipate-co- ω-pentadecalactone), (PGA-co-PDL), NPs were produced using poly (vinyl alcohol) and dioleoyltrimethylammoniumpropane (DOTAP) respectively. The particle size of the anionic NPs was 266.10±20.80 nm and the incorporation of DOTAP resulted in NPs of 244.80±4.40 nm at 15 % DOTAP concentration. The zeta potential (ZP) of 15 % DOTAP NPs was +14.8±0.26 mV. Fluorescently labelled synthetic miRNA (miR-146a) was adsorbed onto the surface of the optimum 15 % DOTAP NPs. The cell viability studies indicated that over 65 % of A549 cells remained viable after 24 h exposure to cationic NPs at a concentration of 1.25 mg/ml. The spray drying process was optimised to produce NCMPs with recovered NPs of 409.7±10.05 nm, yield of 86.05±15.01 % and low moisture content 2.02±0.03 %. The NCMPs produced had a spherical shape and corrugated surface. The in vitro aerosolisation analysis showed a mass mean aerodynamic diameters (MMAD) of less than 6 µm indicating the NCMPs would be deposited in the middle to deep lung region and a fine particle fraction (FPF) of 51.33±2.90 %. Internalisation of miR-146a loaded cationic NPs was observed in A549 cell lines using both fluorescence and confocal microscopy. The miR146a delivered to A549 cells as miR-146a-NPs and miR146a-NCMPs had a dose dependent reduction on target gene repression; interleukin 1 receptor-associated kinase (IRAK1) expression to 40 % and TNF receptor-associated factor (TRAF6) expression to over 20 %. Moreover, the miR-146a biological activity was maintained after spray drying. These findings demonstrate the promise of miR-146a-NPs/NCMPs as a dry powder pulmonary for the treatment of COPD, protecting miR-146a from degradation and enzymatic activity in the lung airways

The Role of Open and Distance Learning in Promoting Professional Training and Development in Tanzania. A Case Study of The Open University Tanzania

This paper unveils the unique role played by ODL in promoting professional training and development in Tanzania. ODL is significantly increasing in its importance in most societies if not all; this is justified by the increasing in enrolment in ODL institutions. In order to cope with the demanding world, individuals need to properly utilize their time. Hence, they opt for ODL institution as a medium of knowledge transmission, since they can benefit from the flexibility that it offers. In the course of this study, the researchers have adopted a qualitative research approach. Where, the main case study institution being The Open University of Tanzania. Respondents from this study have been carefully sampled through a non probabilistic sample size, and these respondents were OUT students only (current and previous). Among all constraints, ICT remains a common barrier among most ODL students in Tanzania, as all the respondents in the study indicated so

The role of HUCB derived stem cells therapy in repair of renal damage and improvement of renal function in cisplatin induced acute renal failure in rats

Acute renal failure (ARF) is a common clinical problem with increasing incidence, serious consequences, unsatisfactory therapeutic options and enormous financial burden to society. The aim is to investigate the role of human umbilical cord blood (HUCB) derived mesenchymal (MSCs) and CD34+ hematopoietic stem cell therapy in repair of renal damage and improvement of renal function in cisplatin-induced ARF model. Forty four rats were divided into 4 equal groups. ARF was induced in 3 groups using cisplatin and was confirmed by an increase in serum urea and creatinine levels after 5 days. On the same day, 2 groups were injected via the tail vein by either MSCs (1x106 cells/rat) or CD34+ hematopoietic cells (5 x105 cells/rat). The third group received intravenous injection of phosphate buffer saline and served as positive control, while the last group was normal control. Renal functions were followed up every 4 days. Thirty-three days after initiation of cisplantin injection, rats were sacrificed, kidneys were extracted for histopathological and immunohistochemical examination for detection of human specific anti-vimentin monoclonal mouse anti body to investigate homing of HUCB stem cells into the damaged renal tissue. Treatment with MSCs and CD34+ cells significantly decreased both serum urea and creatinine induced by cisplatin administration with concomitant improvement in the degree of necrotic and degenerative changes. There was no significant difference in these parameters between MSCs and CD 34+ stem cells treated groups. There was positive reaction for human specific anti-vimentin in 88.9% of animals in MSCs treated rats versus 87.5% in CD34+ cells treated rats. HUCB derived CD 34+ and MSCs accelerate regeneration of renal tubular epithelial cells and lead to reduction of progressive renal injury in cisplatin-induced acute renal failure rats.Keywords: Acute renal failure; CD 34+ cells; Umbilical cord blood; Mesenchymal stem cell

Enhancement of oral bioavailability via solid lipid nanoparticles of anticancer drug dasatinib - An in vitro cytotoxicity and pharmacokinetic study

Objective: Dasatinib (DST) is a BCS Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of DST leads to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of DST. Animal data suggests that the absolute bioavailability of DST is about 14 to 34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid–based drug delivery systems like solid lipid nanoparticles can be used.  Methods: Solid lipid nanoparticles (SLNs) are sub-micron colloidal carriers having a size range of 50–1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. Dasatinib can be conveniently loaded into solid lipid nanoparticles to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of dasatinib suspension. Results: In vitro cytotoxicity study were done by MTT assay method through ATCC cell lines, the percent inhibition was more in SLN when compared with Suspension. The Pharmacokinetics of dasatinib-SLNs after oral administration in male wistar rats was studied. The bioavailability of dasatinib was increased by 2.28 fold when compared with that of a dasatinib suspension. Conclusion: The results are indicative of SLNs as suitable lipid based carrier system for improving the oral bioavailability of dasatinib. &nbsp

Hirschisprung’s disease: Factors Affecting the Outcome at The National Ribat University Hospital, Khartoum, Sudan, 2007 to 2011

Background: Hirschsprung's disease (HSD) remains the most frequent cause of child intestinal obstruction.Objectives: to evaluate the effect of different factors at the final outcome, postoperative complications and the hospital stay of children with HSD.Methodology: It is a retro-prospective analytical observational hospital based study, involving all the cases presented initially to the Paediatric Surgery Centre at the National Ribat University Hospital and confirmed to be a case of HSD. The data were collected using a questionnaire and analyzed by the software SPSS version 17.Results: Sixty four patients were involved in this study with male to female ratio of 5:1. The mean age at the first time of presentation was 9 days and the bulk of the patients seen from the center of Sudan. The emergency presentation accounted for 21.9% of the cases with the delayed passage ofmeconium and constipation as the main presenting symptoms. Complications occur mainly at day 13 post operatively with colostomy prolapse as the commonest type of complications. The age of the patients at the time of Pull Through Procedure (PTP) was ranging between 7 to 72 months and the mean body weight found to be 11.94 kg. Complicationsfollowing PTP occur in 18.8% of the cases, with wound infection accounting for 15.6% of the cases. The total duration of hospital stay post operatively after reversal of colostomy was found to range between 6 and 60 days with a mean of 8.77 days and SD of ± 6.657.Conclusion: The average hospital frequency of HSD in our study is  compared to that encountered in European countries and Northern  American countries. Early diagnosis and treatment is essential for better outcome. Emergency presentation, age and the weight at Pull Through Operation and at the time of closure of colostomy, significantly affect the outcome and prolong the hospital stay.Key words: Hirschsprung's Disease, colostomy, Pull Through Operation

Corn and potato starch as an agar alternative for Solanum tuberosum micropropagation

Potato single nodes were subcultured onto fresh MS medium gelled with 0, 1 and 2 g/l of agar + 40, 50 or 60 g/l of commercial corn and potato starch (CS or PS, respectively). After 4 weeks of culture, the pH of medium supplemented with 50 or 60 g/l of CS or 60 g/l of PS was significantly decreased to 3.91 - 4.00. This reduction coincided with a significant increment in electric conductivity (EC) which was 172 - 214 ìmhos/cm-1 for media containing 50 or 60 g/l of CS, or 60 g/l of PS. Corn and potato starch had no significant effect in plantlet height nevertheless, they significantly increased the number of shoots/explant over the control treatment (2.5) which had 7 g/l of agar. The highest number ofshoots/explant (6.8) was achieved in medium with 50 or 60 g/l of PS + 1 g/l of agar. Plantlets developed on media with 40 g/l of CS or PS had higher shoot fresh and dry weight (p < 0.5) compared to those in thecontrol one. Media with 50, 60 g/l of PS or 60 g/l of CS and 50 g/l of CS + agar at 1 g/l significantly enhanced the percentage of dry weight. Moreover, 92 - 98% of plantlets were acclimatized to the greenhouse conditions regardless the type of gelling agent. The results suggest that the combination of agar and PS or CS could offer a firm support for plant tissues and could be successfully used for potato micropropagation

Production of functional protein hydrolysates from Egyptian breeds of soybean and lupin seeds

Enzymatic hydrolysis is an agro-processing aid that can be utilized in order to improve nutritional quality of protein extracts from many sources. In this study, protein extracts from ungerminated and/or germinated local Egyptian soybean and lupin flours were hydrolyzed using the enzyme papain. The hydrolysis processes were carried out for 2 h and aliquots were withdrawn at different time intervals. We have analysed the protein hydrolysate after 30 min hydrolysis as an example of a partially hydrolyzed protein, and after 120 min as an example of greatly hydrolyzed protein. The hydrolysate (2 h treatment at 80°C and pH 7.4) from both soybean and lupin flour contained significantly decreased trypsin inhibitor activity and urease activity, and a reduced phytate content, which improved the overall protein quality. Hydrolysis caused almost complete inactivation of urease in all soybean and lupin samples regardless if the seeds were germinated or not. High protein content, nitrogen solubility and invitro protein digestibility was shown after hydrolysis. Total protein content (in g/100 g extract) increased in hydrolyzed samples from 48.1 to 51-60 for soybean (dependent on pre-treatment) and from36.8 to 39.9-48.6 for lupin. Total essential amino acid content was also increased in papain hydrolyzed samples, compared to that in raw and germinated legumes. More specifically, the amount of lysine,sulphur amino acids, histidine, and to a certain extent isoleucine and threonine increased in samples from both legume species. All soybean samples exhibited antioxidant activity while in lupin samples,only those subjected to hydrolysis showed activity. Generally, it was clearly observed that the longer the duration of enzymatic hydrolysis (within the time frame of the experiment), the higher the improvement of the nutritional qualit

Laparoscopic Cholecystectomy: A 15-years Experience at a Single Centre, Wad Medani, Sudan

No Abstract