Adjuvant role of Ocimum sanctum hydroalcoholic extract with carbamazepine and phenytoin in experimental model of acute seizures

PurposeThis study assessed adjuvant potential of Ocimum sanctum hydroalcoholic extract (OSHE) with antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT) in maximal electroshock seizure (MES) model in male Wistar rats.Material and MethodsPharmacodynamic effect of OSHE (1000 mg/kg) was assessed through seizure protection potential, neurobehavioral tests and oxidative stress estimation in MES model after 14 days administration of OSHE alone or combination with maximal (M) and sub-maximal (SM) dose of CBZ or PHT. Pharmacokinetic interaction of OSHE with AEDs was also assessed after 14 days of drug treatment.ResultsOSHE per se showed 50% protection against MES-induced seizures. Combination of OSHE with AEDs’ SM dose enhanced its seizure protection potential. Significant reduction in duration of tonic hind limb extension was observed in CBZ-SM + OSHE as compared to control group (p = 0.006). Among neurobehavioral tests in Morris water maze test rats of CBZ-M + OSHE took significantly less time to reach the platform (p = 0.022) and spent more time in target quadrant (p = 0.016) as compared to other groups. Similarly, rats of PHT-SM + OSHE group spent significantly more time in the target quadrant (p = 0.013). In elevated plus maze test, CBZ-M + OSHE had significantly decreased transfer latency compared to other groups (p = 0.013). OSHE alone treated group had significantly lower oxidative stress as compared to other groups. No significant pharmacokinetic interaction was observed between OSHE and AEDs (CBZ, PHT).ConclusionOcimum’s potential of enhanced seizure protection and neuroprotection along with minimal drug interaction with AEDs substantiate its adjuvant role in the management of epilepsy.     

Inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016)

Introduction: Inosine-5′-monophosphate dehydrogenase (IMPDH) is an enzyme involved in the de novo biosynthesis of guanine nucleotides. To date human IMPDH inhibitors have been approved for prevention of organ transplant rejection and as anti-viral agents. More recently, the use of IMPDH inhibitors for other indications including cancer and pathogenic microorganisms has been pursued.

Areas covered: IMPDH inhibitors disclosed primarily in the patent and scientific literature from 2002 to the present are discussed. Several interesting chemotypes that have not been pursued by patent protection are also highlighted.

Expert opinion: Progress has been made in the development of IMPDH inhibitors, particularly compounds that are structurally distinct from mycophenolic acid and nucleoside-based inhibitors. However, clinical progression has been hampered primarily by a limited understanding of the enzyme’s role in disease pathophysiology. Finally, most of the IMPDH inhibitors developed over the past fourteen years fall within a relatively narrow set of chemotypes. This provides opportunities for expanding IMPDH inhibitor chemical space to further evaluate this class of molecular targets.     

The challenges of pharmacokinetic variability of first-line anti-TB drugs

Introduction: Inter-individual variations in the pharmacokinetics (PK) of anti-TB drugs are known to occur, which could have important therapeutic implications in patient management.

Areas covered: We compiled factors responsible for PK variability of anti-TB drugs reported from different settings that would give a better understanding about the challenges of PK variability of anti-TB medications. We searched PubMed data base and Google scholar from 1976 to the present using the key words ‘Pharmacokinetics’, ‘pharmacokinetic variability’, ‘first-line anti-TB therapy’, ‘Rifampicin’, ‘Isoniazid’, ‘Ethambutol’, ‘Pyrazinamide’, ‘food’, ‘nutritional status’, ‘HIV’, ‘diabetes’, ‘genetic polymorphisms’ and ‘pharmacokinetic interactions’. We also included abstracts from scientific meetings and review articles.

Expert commentary: A variety of host and genetic factors can cause inter-individual variations in the PK of anti-TB drugs. PK studies conducted in various settings have adopted different designs, PK sampling time points, drug estimation methodologies. Hence comparison and interpretation of these results should be done with caution More phamacogenomic studies in different patient populations are needed for further understanding.     

Effect of fluidics on corneal endothelial cell density,central corneal thickness,and central macular thickness after phacoemulsification with torsional ultrasound

Aim:To study the relative effects of high and low fluidic parameters on endothelial cell density (ECD), central corneal thickness (CCT), and central macular thickness (CMT) after phacoemulsification with torsional ultrasound.Results:Cumulative dissipated energy was significantly higher in the low flow group (16.44 ± 9.07 vs. 11.74 ± 6.68; P = 0.002). No statistically significant difference was noted between the two groups in the ECD, CCT, CMT, or corrected distance visual acuity at the end of 6 weeks.Conclusions:No significant difference was noted in the postoperative outcome between high and low flow groups. Parameters can be modified to suit the surgeon''s preference, as both high and low flow parameters were found to have comparable postoperative outcomes.