Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).     

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.

Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.

Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process.     

Paraneoplastic cerebellar degeneration as a presenting manifestation of non-Hodgkin’s lymphoma

Background

Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin’s lymphoma.

Objective

We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin’s lymphoma and experienced good clinical response to treatment.

Discussion

As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin’s lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome.

Conclusion

This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required.

     

Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review

Neurosurgical Review - Despite the increasing utility of the endoscopic endonasal approach (EEA) for management of anterior skull base (ASB) pathologies, the optimal treatment strategy for...