Identification of Small Inhibitors for Human Metadherin, an Oncoprotein, through in silico Approach.

AIMS: Cancer is a disease that takes lives of thousands of people each year. There are more than 100 different types of cancers known to man. This fatal disease is one of the leading causes of death today. BACKGROUND: Astrocyte elevated gene-1(AEG-1)/Metadherin (MTDH) activates multiple oncogenic signaling pathways and leads to different types of cancers. MTDH interacting with staphylococcal nuclease domain containing 1(SND1) supports the survival and growth of mammary epithelial cells under oncogenic conditions. OBJECTIVE: Silencing MTDH or SND1 individually or disrupting their interaction compromises the tumorigenic potential of tumor-initiating cells. The aim of our present study was to investigate novel interactions of staphylococcal nuclease domain containing 1 (SND1) binding domain of AEG-1/MTDH with different lead compounds through molecular docking approach using MOE software. METHODS: Molecular docking was done by docking the ChemBridge database against important residues of MTDH involved in interaction with SND1. After docking the whole ChemBridge database, the top 200 interactive compounds were selected based on docking scores. After applying Lipinski's rule, all the remaining chosen compounds were studied on the basis of binding affinity, binding energy, docking score and protein-ligand interactions. Finally, 10 compounds showing multiple interactions with different amino acid residues were selected as the top interacting compounds. RESULTS: Three compounds were selected for simulation studies after testing these compounds using topkat toxicity and ADMET studies. The simulation study indicated that compound 32538601 is a lead compound for inhibiting MTDH-SND1 complex formation. CONCLUSION: These novels, potent inhibitors of MTDH-SND1 complex can ultimately help us in controlling cancer up to some extent.

Efficacy Of Phenytoin In Prevention Of Early Posttraumatic Seizures.

BACKGROUND: The use of anti-epileptic drugs for prophylaxis of early post-traumatic seizures after traumatic brain injury has been very promising. The objective of this study was to determine the outcome of phenytoin in prevention of early post-traumatic seizures in moderate to severe traumatic brain injuries and to compare the frequency of seizures in moderate to severe traumatic brain injury, with phenytoin started within 12 hours and after 12 hours of injury. METHODS: This cross-sectional study was conducted at Department of Neurosurgery, Ayub Medical Institute, Abbottabad from April to October, 2015. All the patients with moderate to severe head injury presenting within 48 hours of injury were included in this study in consecutive manner. Patients were started on phenytoin and observed for early post-traumatic seizures. RESULTS: A total of 163 patients were included in this study with a mean age of 24.69±10.186 years. One hundred and twenty-two (74.8%) were males and rest of 41 (25.2%) were females. A total of 26 (16%) patients had early post-traumatic seizures. 9.89% patients in whom phenytoin was started within 12 hours had seizures, while 23.11% patients in whom phenytoin was started after 12 hours of injury had seizures, the difference being statistically significant (p-value .018).. CONCLUSIONS: Frequency of early post-traumatic seizures is high in patients with moderate to severe head injured patients. Anti-epileptics like phenytoin should be started within 12 hours for seizure prophylaxis.

Comparison Of Simultaneous Versus Delayed Ventriculoperitoneal Shunting In Patients Undergoing Meningocoele Repair In Terms Of Infection.

BACKGROUND: Myelomeningocele is a congenital anomaly of Central Nervous System (CNS) leading to serious sequels related to various systems and organs of the affected patient. Hydrocephalus is a common condition associated with myelomeningocele. Hydrocephalus is seen in 11.8% of children with Myelomeningocele (MMC). This study was conducted to compare the simultaneous vs delayed ventriculoperitoneal shunting in children undergoing myelomeningocele in terms of infection. METHODS: This Randomized Control Trial was conducted at department of Neurosurgery, Ayub Medical College, Abbottabad from 7th March to 7th June 2016. In this study a total of 98 patients with MMC and hydrocephalus were randomly divided into two equal groups. In group A simultaneous MMC repair and VP shunting was performed while in group B MMC repair was done in first and VP shunting was done two weeks postoperatively.. RESULTS: In this study mean age in Group A was 1 years with SD±2.77 while mean age in Group B was 1 years with SD±3.12. In Group A (12%) patients had infection and (88%) whereas in Group B (20%) patients had infection and (80%) patients didn't had infection.. CONCLUSIONS: Simultaneous VP shunting was more effective than delayed VP shunting in children undergoing myelomeningocele in terms of infection.