Effects of Kaempferia parviflora Wall. Ex. Baker on electrophysiology of the swine hearts.

Background & objectives: Pre-clinical studies in swine have demonstrated that a supratherapeutic concentration of sildenafil citrate decreased defibrillation efficacy and facilitated cardiac arrhythmia. We therefore, decided to investigate the effects of Kaempferia parviflora (KP) extract on these parameters in the swine heart. The underlying assumption was that in the heart, KP might be producing effects similar to sildanafil citrate as KP has long been used in southeast Asian traditional medicine to correct erectile dysfunction. Methods: The study was conducted as the defibrillation study, and ventricular fibrillation (VF) induction study. In both studies, the defibrillation threshold (DFT), the upper limit of vulnerability (ULV) and VF threshold were determined before and after KP extract administration. Results: In both studies KP extract at high concentrations (100 and 50 mg/kg) significantly increased the DFT and ULV, without altering the VF threshold. At these concentrations, systolic and diastolic blood pressures were also attenuated. Interpretation & conclusions: High concentrations of KP extract attenuated defibrillation efficacy and increased cardiac vulnerability to arrhythmia in a normal swine heart. When used in appropriate concentrations, its blood pressure lowering effect may be useful in hypertensive states. Further studies need to be done to elucidate its mechanism of action.

Changes in peripheral innervation and nociception in reticular type and erosive type of oral lichen planus.

Background: Oral lichen planus (OLP) is a chronic inflammatory lesion in oral mucosa. Reticular (OLP-R) and erosive (OLP-E) types of OLP are the common forms that have been found in dental clinics. The aim of this investigation is to determine the correlation between neurogenic inflammation and nociception associated with OLP-R and OLP-E. Materials and Methods: The oral mucosal lesions from six patients with OLP-E, four with OLP-R and three with noninflamed oral mucosa, which represent normal mucosa, were identified by morphometric analysis of nerve fibers containing immunoreactive protein gene product (PGP) 9.5. The level of inflammation was measured with hematoxylin and eosin staining and the level of nociception was analyzed with visual analog scale measurement. Results: We found that 1) an increase in peripheral innervation was related to the size of the area of inflammatory cell infiltration from both OLP-R and OLP-E; 2) the pattern of PGP 9.5-immunoreactivity among OLP-R and OLP-E was not significantly different (P=0.23); and 3) the correlation between nociception and an increase in PGP 9.5-immunoreactivity was not found in OLP-E and in OLP-R. Conclusions: Our findings suggest that an increase in peripheral innervation may lead to increased inflammation, which is part of the immunopathogenesis of OLP. Differences in nociception between OLP-R and OLP-E arise from the pathogenesis of each lesion, not from the differences in peripheral innervation.

Reversible acetylcholinesterase inhibitory effect of Tabernaemontana divaricata extract on synaptic transmission in rat CA1 hippocampus.

Background & objectives: Acetylcholinesterase inhibitors (AChE-Is) are used for the treatment of Alzheimer’s disease (AD). These drugs including galanthamine have been shown to modulate synaptic activity in hippocampus and improve memory processes. Although Tabernaemontana divaricata extract (TDE) has been used as traditional medicine for various pharmacological effects, its effect in enhancing cholinergic activity provides additional benefit to its known effects. We investigated whether TDE can modulate the synaptic function in hippocampus and compared its effects to those of galanthamine. Methods: Hippocampal slices were prepared from male wWistar rats, functional effects of TDE were characterized by using pharmacological tools and extracellular recordings of field excitatory postsynaptic potentials (fEPSPs). Results: TDE significantly reduced fEPSPs. The fEPSPs reduction was prevented by atropine, but not pancuronium. These TDE effects were similar to those of galanthamine. Interpretation & conclusions: Our findings indicate that TDE can effectively modulate synaptic responses in the hippocampus similar to galanthamine, suggesting that this traditional medicine could be beneficial in ageing with ACh deprivation in the brain.

Ethnobotany & ethnopharmacology of Tabernaemontana divaricata.

Tabernaemontana divaricata a common garden plant in tropical countries has been used as a traditional medicine. However, no recent review articles of T. divaricata, particularly discussing its pharmacological properties, are available. This review presents the ethnobotany and ethnopharmacology of T. divaricata as well as its potential therapeutic benefits especially of the alkaloidal and non-alkaloidal constituents. Included, are the characteristics of 66 alkaloids isolated and identified from T. divaricata. Non-alkaloids including the enzymes, pyrolytic oil, hydrocarbons, terpenoid and phenolic acids are also documented. Chemotaxonomic aspects of each alkaloid as well as information regarding the pharmacology of crude extracts and individual alkaloids from T. divaricata have been assembled and appraised. The beneficial properties of T. divaricata are antioxidant, anti-infection, anti-tumour action, analgesia and the enhancement of cholinergic activity in both peripheral and central nervous systems. The augmentation of cholinergic function may be of therapeutic benefit for many neurodegenerative diseases, particularly myasthenia gravis and Alzheimer's disease.

Effects of combined sildenafil-nitric oxide donor on defibrillation efficacy.

BACKGROUND: A previous study demonstrated that supra-therapeutic concentration of sildenafil citrate attenuates defibrillation efficacy. However, the effect of combined sildenafil and NTG administration on defibrillation efficacy is not known. OBJECTIVE: The present study investigated whether sildenafil administration at the therapeutic level increases the defibrillation threshold (DFT) when combined with NTG. MATERIAL AND METHOD: Twenty-four pigs (20-25 kg) were randomized into four groups. After the control DFT was obtained, a stock solution of 50-mg (group 1, therapeutic concentration) and 100-mg (group 2, supratherapeutic concentration) of sildenafil, and 100-mL of saline (groups 3 and 4) were infused at 2 mL/min. Then, NTG was administered in groups 1-3 at 5 microg/min, with an increment of 5 microg/min every 5 min. The DFT was determined again after NTG was infused for 20 minutes. RESULTS: In group 1, the DFT (402 +/- 33V, 11 +/- 2J) was not different from the control (404 +/- 28V, 11 +/- 2J). In group 2, the DFT (521 +/- 18V, 19 +/- 1J) was higher (p < 0.004) than that in the control group (444 +/- 31V, 14 +/- 2J). Saline did not alter the DFT either individually or in combination with NTG. CONCLUSION: Supratherapeutic dose of sildenafil-NTG combination significantly increased the DFT (17% of peak voltage, 37% of total energy). This effect on DFT appears to be driven by sildenafil and not NTG.

Electrophysiological concept of ventricular defibrillation mechanism.

Sudden cardiac death is a major health problem in most industrialized countries around the world including Thailand. It is mainly caused by ventricular fibrillation (VF). Currently, defibrillation is the only effective clinical treatment of this fatal arrhythmia. Although defibrillation mechanism has been investigated extensively for many decades, its definite mechanism is still debated. It is known that understanding the basic mechanism of defibrillation is essential to develop better treatment of VF: In the present article, seven hypotheses commonly proposed as the mechanism of ventricular defibrillation are reviewed. Since research in the field of defibrillation mechanism is dynamic, the present review is to update the information to clinicians and basic investigators on the mechanism of defibrillation available to date.