The efficacy and safety of first-line anti-seizure medications as substitution therapy for children with drug-resistant epilepsy: a randomized controlled trial protocol

Although many anti-seizure medications (ASMs) are available, treatment failure, known as drug-resistant epilepsy (DRE), still occurs in around 30% of children with epilepsy. Second-line ASMs are usually used as substitution therapy in DRE to control seizures, although international consensus is not available yet. Previous studies focus on comparing the ASMs, whether as add-on or substitution therapy, mainly conducted in newly diagnosed epilepsy. However, the study that investigated first-line ASMs as substitution therapy compared to second-line ones, particularly among DRE children, is still lacking. A randomized controlled trial (RCT) enrolling 102 participants, aged 1–18, at three referral hospitals in Indonesia will be conducted, dividing them into intervention and control groups. The intervention group will be treated with first-line ASMs as the substitution therapy, while the other in the control group will get second-line ASMs. The primary outcome measure is the proportion difference of responders between groups who get first-line and second-line ASMs in 14 weeks of intervention.Clinical trial registration: ClinicalTrials.gov, identifier NCT05697614

Progeria and accelerated cardiovascular aging

Hutchinson–Gilford Progeria syndrome (HGPS) is characterized by accelerated aging leading to death in the teen years, usually due to severe coronary and/or carotid disease. The clinical presentation includes stunted growth, alopecia, loss of subcutaneous fat, osteoporosis, and cardiovascular disorders occurring in late childhood and the teen years including hypertension and accelerated vascular aging that precipitates myocardial infarction and cerebrovascular attacks. The disease is a nuclear laminopathy, due to a Lmna gene mutation. The aberrant protein (Progerin) accumulates in and distorts the nuclear envelope. We review the genetic and biochemical mechanism of HGPS; the clinical presentation with special attention to the cardiovascular pathology and complications; current therapeutic developments to address the disease; and the results of the clinical trials attempting to translate basic research insights into therapeutic benefit. An understanding of HGPS may lead to better treatment of other age-related disorders, particularly cardiovascular diseases

In search of suitable extraction technique for large scale commercial production of bioactive fraction for the treatment of diabetes: The case Diospyros melanoxylon Roxb.

Diospyros melanoxylon Roxb. (D. melanoxylon) belongs to the family Ebenaceae and its leaves are very well known for making beedi throughout the World. The current study estimated the comparative extraction technique and its in-vitro antidiabetic prospective of the leaves of D. melanoxylon. Qualitative phytochemicals analysis of the samples from D. melanoxylon was carried out for the detection of secondary metabolites. Total phenolics, flavonoids, triterpenoids and tannins content of D. melanoxylon were estimated using colorimetric assay. Microwave-assisted extraction (MAE) technique with a low carbon output was observed for the speedy extraction of bioactive compounds obtained from Diospyros melanoxylon leaf extract. MAE produced a maximum yield of bioactive compounds which was found to be more efficient than ultrasound, soxhlet and maceration extraction. Qualitative HPLC analysis was performed for bioactive compounds. The in-vitro antidiabetic assay was performed using α-amylase and α-glucosidase inhibitory activity. In conclusion, the fractions exhibited the concentration-dependent inhibitory effect with significant (P < 0.0001) result. So the above performance might be accountable for the antidiabetic activity of D. Melanoxylon leaf extract due to presence of bioactive compounds. Keywords: D. melanoxylon, Extraction techniques, HPLC, Polyphenolics, Antidiabeti

ANTIOXIDANT AND ANTICANCER ACTIVITY OF EXTRACT AND FRACTIONS OBTAINED FROM DIOSPYROS MELANOXYLON ROXB. LEAVES AND CORRELATION WITH THEIR POLYPHENOLIC PROFILES

Objective: The current study evaluates the antioxidant and cytotoxic prospective of the leaves from Diospyros melanoxylon Roxb. (D. melanoxylon).Methods: Qualitative phytochemical analysis of the samples from D. melanoxylon was carried out for the detection of secondary metabolites. Total content of flavonoids, phenolics, triterpenoids, and tannins in D. melanoxylon was evaluated using colorimetric assay. Qualitative analysis of polyphenolic compounds was performed using HPLC method. The antioxidant activity was examined by assessing the various free radical scavenging assays. Five human cancerous cell lines (HeLa, MCF-7, HCT-116, PC-3, and HEK293), one rat colon cancer cell line (RCC 45) and two normal cell lines (NKE and WI-38) were used for evaluating the anticancer activity through methylene blue assay.Results: The results indicated that ethyl acetate fraction (EAF) and aqueous fraction (AQF) exhibited the remarkable content of flavonoids, phenolics, triterpenoids, and tannins. Both EAF and AQF have cytotoxic activity with significant IC50 values but not showed significant antioxidant activity. However, the most powerful anticancer activity was recorded by EAF followed by AQF in a dose-dependent manner. It was also revealed that EAF and AQF were biocompatible with the normal cell lines.Conclusion: Our principal finding exhibited a potent anticancer activity. Furthermore, it was also indicated that samples contain secondary metabolites like flavonoids, phenolics, triterpenoids, and tannins. We suggest that the further investigation on this herb is effective against various types of ailments including cancer.Keywords: Diospyros melanoxylon Roxb., Scanning Electron Microscopy (SEM), High-Pressure Liquid Chromatography (HPLC), Polyphenols, Antioxidant, Anticance