Friedelin and Glutinol induce neuroprotection against ethanol induced neurotoxicity in pup's brain through reduction of TNF-α, NF-kB, caspase-3 and PARP-1.

Ethanol administration triggers an inflammatory response that leads to a complex series of immune responses including the release of an excessive amount of inflammatory mediators particularly tumor necrosis factor (TNF-α) and nuclear factor-kB (NF-KB) which produce a large amount of reactive oxygen species. The inflammatory-induced cytotoxicity is increased when the PI3-kinase/Akt pathway is inhibited. Some studies have also shown that ethanol suppresses the PI3-kinase signaling pathway induced by receptor activation. Friedelin and Glutinol belong to pentacyclic triterpenoid class and are known for their anti-inflammatory and antioxidant properties. The present study was aimed to elucidate the effects of these phytoconstituents on one of the key ethanol-induced neuronal damage pathways. The pups having (5-7 g average body weight) were used and randomly divided into groups. The control and ethanol treated pups were administered 0.9% normal saline while treated pups received glutinol and friedelin (30 mg/kg subcutaneously) respectively. After four hours all the experimental animals were sacrificed and their brains were collected carefully for protein expression analysis of p-Akt, TNF-α, NF-KB, caspase-3 and PARP-1 employing immunoblotting technique. Hemolytic, DNA protection, chelating power and ß-carotene assays results revealed that freidelin and glutinol are safe for parenteral administration. Glutinol administration with ethanol significantly abridged the ethanol induced over expression of TNF-α, caspase-3 and PARP-1 in pup's brain. Similarly, freidelin attenuated the neurodegeneration by inhibiting the ethanol induced p-JNK and NF-kB expression in pups' brain. This protection may be attributed to the revival of p-Akt signaling for cell survival. It is concluded that the present study demonstrates the neuro-protective effects of friedelin and glutinol via modulating the capase-3 and PARP-1 expression and modulating the neuronal apoptotic pathways.

Prevalence and treatment of neurological and psychiatric disorders among tertiary hospitals in Pakistan; findings and implications.

INTRODUCTION: Mental health and neurological disorders are prevalent in Pakistan. However, there are considerable concerns with their management due to issues of access, availability of trained personnel and stigma alongside paucity of such data. Consequently, there is a need to document current treatment approaches starting with tertiary hospitals in Pakistan where patients with more severe mental and neurological disorders are typically treated. Subsequently, use the findings to help direct future policies and initiatives. METHODS: Multi-centered, cross-sectional, prospective study principally evaluating current medicine usage among patients attending tertiary hospitals in Pakistan with psychiatric and neurological disorders. In addition, possible factors contributing to the prevalence of these disorders in this population to help with future care. All 23 tertiary care hospitals in the ten major Districts in Pakistan were included, which cover 75% of the population. RESULTS: 57,664 patients were evaluated of which 35.3% were females. Both females and males had multiple brain disorders and multiple co-morbidities. Schizophrenia was the most prevalent disorder overall among both females (25.2%) and males (30.4%). A median of six medicines were prescribed per patient, with antipsychotics and antidepressants the most prescribed medicines. Clozapine was the most prescribed medicine in males (12.25%) and females (11.83%) including for psychiatric disorders, with sodium valproate the most prescribed medicine in epilepsy in males (42.44% of all anti-epileptic medicines) as well as females (46.38%). There was a greater prevalence of both disorders among the lower classes. A greater prevalence of schizophrenia was seen in patients abusing alcohol and smokers. The divorce rate was higher among the studied patients and the prevalence of depression was higher among the widowed population. CONCLUSIONS: There were concerns with the quality of prescribing including the extent of polypharmacy as well as possible overuse of clozapine especially in patients with epilepsy, both of which need addressing.