Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.

OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.

Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for tumor imaging and treatment response assessment-preclinical evaluation and preliminary human results.

The present study describes the successful radiolabeling of [99mTcO(-) 4 ] with doxorubicin, and the resultant product was formulated in to a ready-to-label lyophilized single vial kit preparation for convenient use in a routine clinical setting. The radiolabeled preparation of [99mTc]-doxorubicin exhibited a high radiolabeling efficiency of more than 95.0%, serum stability for up to 24 h, and shelf-life of lyophilized cold kits was more than 6 months. Animal imaging data in tumor-bearing mice demonstrated that [99mTc]-doxorubicin accumulated in the tumor site with high target (tumor) to non-target (contra-lateral thigh) ratio (3.2 ± 0.5). The ratio decreased to 1.2 ± 0.6 indicating a good response on follow up imaging performed after 2 weeks of doxorubicin treatment. [99mTc]-doxorubicin scintigraphic data in human volunteers supported the hepato-renal excretion of the radiotracer as reflected by the increased accumulation of the radiotracer as a function of time in intestine, kidneys, and urinary bladder. Further, imaging in patients (very limited number) indicated that the technique may be useful in the detection of active sarcoma and post treatment (surgery/chemotherapy) remission or absence of the disease. The technique, however, needs validation through further preclinical evaluation and imaging in a larger number of patients.

Technetium-99m ciprofloxacin imaging in the diagnosis of postsurgical bony infection and evaluation of the response to antibiotic therapy: A case report.

The use of radiolabelled antibiotics is fast emerging as a promising diagnostic test for the detection of infective lesions, because of their specific binding to the bacterial component. Ciprofloxacin is a broad-spectrum antibiotic that has been used as a radiolabelled antibiotic in both the diagnosis of infections in rabbits and in clinical trials on humans. The diagnosis of skeletal microbial infections remains a challenge, especially in orthopaedic patients with implants. We present a case report of a patient with undiagnosed and unrelenting pain in the lower third of the left leg, which had persisted for 6 months. A novel scintigraphy, which was developed in-house using a 99mTC ciprofloxacin single vial kit, was used for diagnosing the active bacterial infection. A 99mTC methylene diphosphonate bone scan was also performed to locate precisely the site of the lesion. Gradually increasing concentrations of both the radiotracers confirmed the presence of active bacterial infection in the distal third of the left tibia. Follow-up scanning after antibiotic therapy showed the disappearance of the pooling of 99mTC ciprofloxacin, indicating a good response. Therefore, 99mTC ciprofloxacin has good diagnostic and prognostic applications in deep-seated covert skeletal microbial infections. However, the persistence of a focal concentration detected by the 99mTC methylene diphosphonate scan was attributed to the inflammatory and not the infective pathology.