Effects of Kaempferia parviflora Wall. Ex. Baker and Sildenafil Citrate on cGMP Level, Cardiac Function, and Intracellular Ca2+ Regulation in Rat Hearts

ABSTRACT:: Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.     

Epidemiology of Malaria in Thailand

Background : In spite of significant achievements in malaria control in the past two decades, about 150,000 malaria cases still occur in Thailand each year. Although most short-term visitors to Thailand stay in malaria-free areas, an increasing number of more adventurous travelers are exposed to the disease.
Method : Since 1987, the Malaria Division of the Thai Ministry of Public Health has maintained a computerized database that includes all malaria cases recorded at malaria clinics, government health institutions, and private hospitals nationwide. In this article, we analyze the 1992 data.
Results : The provinces of Trad, Tak, and Kanchanaburi had the highest incidence of locally transmitted cases. Trad Province was also responsible for the highest number of imported cases. The highest incidence rate was found to be 426.5 per 1000 persons per year in a group of villages in Maesod District, Tak Province. Districts and provinces with ≥ 20 cases per 1000 persons per year are listed in this report. Peak transmission seasons and species prevalence of different endemic areas are described. Analysis of case investigation, a part of this database, indirectly supported the presence of mefloquine resistant Plasmodium falciparum strains on the Thai-Cambodian border.
Conclusions : This paper describes the characteristics of malaria in different parts of Thailand and pinpoints areas with significant transmission. However, in accordance with the present policy of the Thai national malaria control program, we do not recommend chemoprophylaxis, but we do strongly encourage personal protection, early diagnosis, and prompt treatment.     

Bioavailability and pharmacokinetic comparison between generic and branded azithromycin capsule: a randomized, double-blind, 2-way crossover in healthy male Thai volunteers

BACKGROUND: Azithromycin is a semisynthetic azalide antibiotic with extensive tissue penetration and a prolonged t(12). It is used once daily for 3 days in the treatment of a number of bacterial infections. However, based on a literature search, information concerning its pharmacokinetic properties, including the relative bioavailability of a newly developed generic capsule formulation compared with an established branded one in the Thai population, has not been reported. OBJECTIVE: The aim of this study was to compare the relative bioavailability and other pharmacokinetic properties of a newly developed generic capsule formulation of azithromycin with those of an established branded formulation in healthy male volunteers in Thailand. METHODS: A randomized, double-blind, 2-way crossover study was performed in healthy male Thai volunteers under fasting conditions with a washout of 30 days between the study periods. A single dose of 2 x 250-mg azithromycin capsules was orally administered, and blood samples were collected over a period of 120 hours. Plasma azithromycin concentrations were determined using a validated high-performance liquid chromatography method with fluorescence detection after derivatization with 9-fluorenylmethyloxycarbonyl chloride. A plasma concentration-time curve was generated for each volunteer from which the C(max), T(max), AUC(0-Iast), AUC(0-infinity), t(1/2), and kappa(e) were determined using noncompartmental analysis. Bioequivalence was defined using regulatory requirements set forth by Thailand, Association of Southeast Asian Nations, and the US Food and Drug Administration (bioequivalence acceptance range, 0.80-1.25). RESULTS: A total of 14 volunteers completed the study. The mean age of volunteers was 20.8 years (range, 19-23 years), and the mean body weight was 62.8 kg (range, 50.6-70.0 kg). The mean (SD) T(max), C(max), AUC(0-last), and AUC(0-infinity) values after administration of the generic and branded formulations were 1.46 (0.41) versus 1.54 (0.41) hours, 425.23 (208.45) versus 431.75 (198.16) ng/mL, 3919.77 (1549.65) versus 4344.79 (1654.98) ng . h/mL, and 4027.05 (1839.13) versus 4515.53 (2203.87) ng . h/mL, respectively. The relative bioavailability of the generic and branded formulations were 1.00 (0.17). The mean (SD) t1/2 values after administration of the generic and branded formulations were 26.43 (10.92) and 28.10 (13.13) hours, respectively. The analysis of variance results of the natural logarithm (In) -transformed values found no significant effect of formulation, period, or sequence on the studied pharmacokinetic parameters. The 90% CIs of the treatment ratios for the Intransformed values of C(max), AUC(0-last), and AUC(0-infinity) were 0.82 to 1.11, 0.91 to 1.06, and 0.91 to 1.08, respectively. All were within the standard bioequivalence acceptance range of 0.80 to 1.25. No adverse events were reported in this study. CONCLUSIONS: In this small study in a selected population of healthy male Thai volunteers, the C(max) and AUC were not statistically significantly different between generic and branded formulations of a single, 2 x 250-mg dose of azithromycin capsules. The generic and branded formulations were found to be bioequivalent. Both formulations were well tolerated.     

The cycle for a Siphoviridae-like phage (VHS1) of Vibrio harveyi is dependent on the physiological state of the host

In a previous report, we isolated Vibrio harveyi (VH) 1114 together with its bacteriophage, VHS1, from a black tiger shrimp-rearing pond. The VHS1 has its lysogenic relationship to the VH1114 host as either true lysogen (TL) or pseudolysogen (PL). The characters of TL are based on the extrachromosomal existence of the VHS1 phage genome in the VH host which also simultaneously produces the VHS1 phage particles and is resistant to super-infection. The original VH1114 host exhibits a clear plaque after infection with VHS1 phage. The PL, on the other hand, exhibits a turbid plaque and does not possess the phage genome but shows toleration to the phage infection. Maintaining the PL in artificial seawater (ASW) for 1h causes the PL to be sensitive to VHS1 infection and results in clear plaques as in the original clone. A chloramphenical-added-ASW treated pseudolysogen clone (PLC), however, prevented VHS1 infection. It is postulated that the infection of VHS1 phage is regulated with a phage binding receptor which supposed to be inducible.     

Biphasic effects of Morus alba leaves green tea extract on mice in chronic forced swimming model

In this study, the effects of an aqueous extract of Morus alba leaves green tea (ME) on mouse behaviors (depression, anxiety, climbing activity and thermal response), muscle coordination and muscle strength were studied. Male IRC mice received a single intraperitoneal injection of either the ME, desipramine or diazepam. Thirty minutes after injection, the mice were tested in all experimental models. A significant antidepressant-like effect could be detected in the animals receiving either 100 or 200 mg/kg ME. The effect of 200 mg/kg ME in decreasing the immobility time was comparable to 10 mg/kg desipramine. With higher dose (1000 mg/kg), a significant increase in immobility time could be observed. In the elevated plus maze, no increase in time in the open arm could be observed in mice treated with ME at either 100 or 200 mg/kg. However, high doses of ME (500 or 1000 mg/kg) decreased both time in the open arm and the number of entries in the maze. No change in thermal response could be seen in mice treated with ME at doses up to 500 mg/kg, however, at 1000 mg/kg, the response time to heat was increased significantly. The ME at either 500 or 1000 mg/kg also decreased muscle coordination, strength and climbing activity significantly when compared with the control. This study suggests that ME possesses an antidepressant- without an anxiolytic-like effect, however, at high doses, the extract might show the sedative effect and alter other functions such as muscle strength, animal activity in the maze and pain response.     

Sodium fluoride mouthrinse used twice daily increased incipient caries lesion remineralization in an in situ model

Objectives

To investigate the remineralizing effects of fluoride mouthrinses used at different times and frequency in addition to fluoride toothpaste.

Methods

A randomized crossover single blinded study comprised 4 experimental phases of 21 days each. Twelve orthodontic volunteers were fixed with an orthodontic bracket containing an artificial carious enamel slab, which was from the same tooth in all 4 phases, and were randomly assigned to the following groups: (1) brushing with F toothpaste 2× per day (F- brush), (2) F- brush + rinsing with 0.05% NaF (F- rinse) after lunch, (3) F- brush + F-rinse before bedtime, and (4) F- brush + F- rinse 2× per day. Mean mineral gain after each phase was determined from mineral density profiles obtained using Micro-CT.

Results

The mean mineral gain in all treatments with F- brush and F-rinse were significantly greater than those in F- brush (p < 0.05). Moreover F- rinse 2× per day increased lesion remineralization more than F- rinse once a day.

Conclusions

The twice-daily use of 0.05% NaF mouthrinse combined with twice-daily regular use of fluoride toothpaste resulted in the greatest remineralization of incipient caries. These data indicate that rinsing frequency is a factor affecting the effectiveness of fluoride mouthrinse.

Clinical significance

The rinsing frequency of NaF mouthrinse, when used with fluoride toothpaste, also affects the remineralization. This finding, if confirmed by a clinical study, would lead to a new recommendation for fluoride mouthrinse used in high caries risk patients who could benefit from using it twice a day.     

Indirect immunoperoxidase test for the diagnosis of leptospirosis

Leptospirosis is a widespread zoonotic disease that affects all mammals, including humans, in different parts of the world. Clinical recognition of leptospirosis is challenging, and the definitive serologic diagnosis assay, the microscopic agglutination test (MAT), is time-consuming and difficult to conduct. In this study, an indirect immunoperoxidase (IIP) test to detect Leptospira-specific antibodies in human serum samples was developed. The efficacy of the IIP was compared with the indirect immunofluorescent assay (IFA) and MAT. A total of 368 human serum samples were analyzed by MAT, IFA, and IIP. Using a MAT titer of > or = 1:100 as the gold standard, the sensitivities for the detection of Leptospiral antibodies at a titer of 1:200 were 94.7% by IFA and 93.6% by IIP; specificities were 95.3% by IFA and 94.9% by IIP; and accuracies were 95.1% by IFA and 94.6% by IIP. With a titer of 1:400, the sensitivity, specificity, and accuracy were 86.2%, 98.9%, and 95.7% by IFA, respectively; whereas, for the IIP, the sensitivity was 85.1%, specificity 98.5%, and accuracy 95.1%. A further evaluation of this test with 80 unknown-febrile-disease sera was also included. We found that the sensitivity and specificity of this test were 100% and 76.8%, respectively. Therefore, the IIP test is a potentially valuable tool for the diagnosis of leptospirosis.     

Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal

Chili and turmeric are common spices in indigenous diets in tropical regions. Being rich in phenolic compounds, they would be expected to bind iron (Fe)(3) in the intestine and inhibit Fe absorption in humans. Three experiments were conducted in healthy young women (n = 10/study) to assess the effect of chili and turmeric on Fe absorption from a rice-based meal containing vegetables and iron fortified fish sauce in vivo. Iron absorption was determined by erythrocyte incorporation of stable isotope labels ((57)Fe/(58)Fe) using a randomized crossover design. Addition of freeze-dried chili (4.2 g dry powder, 25 mg polyphenols as gallic acid equivalents) reduced Fe absorption from the meal by 38% (6.0% with chili vs. 9.7% without chili, P = 0.0017). Turmeric (0.5 g dry powder, 50 mg polyphenols as gallic acid equivalents) did not inhibit iron absorption (P = 0.91). A possible effect of chili on gastric acid secretion was indirectly assessed by comparing Fe absorption from acid soluble [(57)Fe]-ferric pyrophosphate relative to water soluble [(58)Fe]-ferrous sulfate from the same meal in the presence and absence of chili. Chili did not enhance gastric acid secretion. Relative Fe bioavailability of ferric pyrophosphate was 5.4% in presence of chili and 6.4% in absence of chili (P = 0.47). Despite the much higher amount of phenolics in the turmeric meal, it did not affect iron absorption. We conclude that both phenol quality and quantity determine the inhibitory effect of phenolic compounds on iron absorption.     

An open label, randomized comparative study of levofloxacin and amoxicillin/clavulanic acid in the treatment of purulent sinusitis in adult Thai patients

The objective of the study was to compare the clinical efficacy and bacteriological response of levofloxacin and amoxicillin/clavulanic acid (co-amoxiclav) in the treatment of purulent maxillary sinusitis. Sixty patients randomly received either levofloxacin 300 mg orally once daily (LEV group) or co-amoxiclav 625 mg three times a day (COA group) for 14 days. Thirty four patients were in the LEV group and 26 patients were in the COA group. The mean total symptom score was significantly decreased after treatment and was comparable between both groups. Radiological improvement was 61.8% in the LEV group (41.2% resolution, 20.6% improvement) and 61.5% in the COA group (26.9% resolution, 34.6% improvement). Pretreatment maxillary antral aspiration cultures were positive in 28 patients (82.4%) in the LEV group and 20 patients (76.9%) in the COA group. Bacteriological eradication was 78.5% in the LEV group and 70.0% in the COA group, which was not significantly different. In the LEV group, the eradication rate for major pathogens of acute sinusitis was 100% for H. influenzae (both betalactamase +ve and -ve), 100% for S. pneumoniae and S. aureus, 100% for Neisseria species, and 66.7% for P. aeruginosa. The eradication rate in the COA group was 75% for H. influenzae (both betalactamase +ve and -ve), 100% for S. pnumoniae and S. aureus, 50% for Neisseria species, and 0% for P. aeruginosa. There were no significant changes in vital sign measurements or hemato-biochemical parameters at the end of treatment as compared to baseline values, in both groups. Adverse events were found in 8.8% of patient in the LEV group and in 7.7% of patients in the COA group. Adverse events included nausea, abdominal pain, and diarrhea. All the adverse events in both groups were mild and resolved spontaneously. This study demonstrated that levofloxacin 300 mg orally once daily was as effective and safe as amoxicillin/clavulanic acid 625 mg three times a day in the treatment of maxillary sinusitis, either acute or acute exacerbation. Both drugs showed bacteriological efficacy that was not significantly different. The once daily dosage regimen is more applicable, convenience and has better compliance.