In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

Driving under light and dark conditions: effects of alcohol and diazepam in young and older subjects

Objectives: Driving at night time increases accident risk due to visual conditions, fatigue and impaired performance. In addition, the use of alcohol and benzodiazepines may enhance the risks related to night-time driving. We studied these aspects of traffic safety in a simulated driving test with young and older drivers. Methods: In a double-blind, crossover, placebo-controlled study, nine young subjects, aged 22–24 years, performed simulated driving in both `light' and `dark' conditions, before and 1.5 h and 4 h after 0.8 g · kg⁻¹ ethanol (EOH) or 15 mg diazepam (DZ). Further, nine older subjects, aged 55–77 years, were similarly tested, but their EOH dose was 0.7 g · kg⁻¹ and the DZ dose was 10 mg. The tests were vigilance assessment on visual analogue scales (VAS), simulated driving under light and dark conditions for 6 min each and digit symbol substitution (DSS). Results: In the young subjects, both EOH and DZ similarly impaired DSS, with DZ causing more subjective drowsiness, clumsiness, mental slowness and poor overall performance than EOH. During simulated driving, both EOH and DZ impaired simple and complex tracking (EOH>DZ) and prolonged reaction times (EOH=DZ). Impairment of performance was practically identical under light and dark conditions. In the older subjects, objective performance on DSS was poorer (−30%) than that of the young ones, and subjective impairment was marginal. During simulated driving, the baseline levels of variables in older subjects showed definite impairment (errors +100% to +500%) when compared with young subjects. Active drugs impaired several variables (EOH>DZ), but the statistical significances were fewer than in young subjects. Increase in reaction errors reached statistical significance, especially while driving in the dark. Otherwise the driving results in light and dark were not notably different. Conclusion: Young subjects drew good baselines but were sensitive to EOH and DZ, whilst the older subjects showed poor baselines but were less sensitive to EOH and DZ. Although the baseline driving and responses to treatments were different in young and older subjects, their driving and psychomotor impairment were unaffected by light conditions. Received: 10 November 1999 / Accepted in revised form: 25 April 2000     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.     

Familial occurrence of abdominal aortic aneurysm

BACKGROUND: A family history of abdominal aortic aneurysm has been reported to increase the risk for developing the disease. OBJECTIVE: To determine the risk for abdominal aortic aneurysm in first-degree relatives of patients with the disease. DESIGN: Cross-sectional ultrasonographic screening study. SETTING: University Central Hospital, Helsinki, Finland. PATIENTS: 238 of 325 living first-degree relatives of patients having surgery for abdominal aortic aneurysm (age > 50 years; 98 men and 110 women) and 281 controls (135 men and 149 women) without a family history of abdominal aortic aneurysm. MEASUREMENTS: Ultrasonography was used to measure aortic diameter in 101 male relatives and 140 female relatives (241 of the 325 persons at risk [74%]) and in 281 controls. RESULTS: Three siblings had already undergone surgery for abdominal aortic aneurysm. Eleven siblings (all brothers) (11 of 101 [10.9%]) had ultrasonographic evidence of abdominal aortic aneurysm (aortic diameter > 30 mm). In the control group, 2 men (1.5%) and 2 women (1.3%) had an aneurysm. Thirty siblings and no controls had dilatation of the abdominal aorta (aortic diameter, 20 to 29 mm). Neither the age nor the sex of the proband affected risk for developing abdominal aortic aneurysm among first-degree relatives. Family history increased the risk for an aneurysm by 4.33-fold (95% CI, 1.32-fold to 14.23-fold), male sex increased the risk by 12.21-fold (CI, 2.63-fold to 56.64-fold), and age (by decade) increased the risk by 1.93-fold (CI, 1.15-fold to 3.25-fold). CONCLUSION: Aging brothers of patients with known abdominal aortic aneurysm have the highest risk for developing the disease; the prevalence of the disease in siblings older than 60 years of age is 18%.     

Concentrations of metronidazole and tinidazole in female reproductive organs after a single intravenous infusion and after repeated oral administration

Summary Concentrations of metronidazole and tinidazole in serum and gynecological organs were analyzed after a single 500 mg intravenous infusion and after three days of treatment with 400 mg t.i.d. of metronidazole or 500 mg b.i.d. of tinidazole. The studies were performed in 67 patients subjected to hysterectomy and/or oophorectomy because of myomatosis uteri, carcinoma uteri or endometriosis. At the time of organ removal (about 30 min after infusion), metronidazole and tinidazole levels in serum were 14.5 ± 0.45 mg/l and 12.3 ± 0.38 mg/l, respectively. Concentrations of both drugs in the uterus and Fallopian tube were about the same as the simultaneous serum levels and concentrations in the ovaries about 55% thereof. At steady-state, the concentrations of tinidazole in serum (23.5 ± 1.0 mg/l) were remarkably higher than those of metronidazole (13.5 ± 0.84 mg/l) about three hours after the last oral dose. Drug concentrations in organs of the female reproductive tract were 70 to 100% those of the simultaneous serum levels.

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Konzentrationen von Metronidazol und Tinidazol in weiblichen Genitalorganen nach intravenöser Einzelinfusion und wiederholter oraler Gabe

Zusammenfassung Die Konzentrationen von Metronidazol und Tinidazol in Serum und Genitalorganen wurden nach einer intravenösen Einzelinfusion von 500 mg sowie nach dreitägiger oraler Behandlung mit 400 mg Metronidazol dreimal täglich oder 500 mg Tinidazol, zweimal täglich, bestimmt. Die Untersuchungen wurden bei 67 Patientinnen durchgeführt, bei denen eine Hysterektomie und/oder Oophorektomie wegen Myomatosis uteri, Uteruskarzinom oder Endometriose vorgenommen wurde. Zum Zeitpunkt der Organentnahme (etwa 30 min nach Infusion) betrugen die Metronidazol-und Tinidazolspiegel im Serum 14,5 ± 0,45 mg/l bzw. 12,3 ± 0,38 mg/l. Die Konzentrationen der beiden Medikamente im Uterus und in der Tube entsprachen den gleichzeitig bestimmten Serumspiegeln; die Konzentrationen in den Ovarien lagen bei etwa 55% der Serumspiegel. Im Steady state, etwa drei Stunden nach der letzten oralen Dosis, waren die Serumkonzentrationen von Tinidazol mit 23,5 ± 1,0 mg/l erheblich höher als die Metronidazolserumspiegel (13,5 ± 0,84 mg/l). Die Konzentrationen der Medikamente in den weiblichen Genitalorganen lagen bei 70 bis 100% der simultanen Serumspiegel.

     

Angiographic findings in patients exhibiting ischemia after oral dipyridamole

We have assessed the angiographic features of a group of 37 patients given oral dipyridamole and 37 patients given matching placebo. Both groups represented severe coronary arterial disease and were studied prior to bypass surgery. Six patients (16%) had angina and 13 patients (35%) had electrocardiographic changes after dipyridamole. All the patients in the control group were nonresponders. In the group given dipyridamole the patients responding with angina had significantly more compromised collaterals than the patients without chest pain (P = 0.021). The same applied to the patients with electrocardiographic changes versus those with no electrocardiographic changes (P = 0.034). No differences between responders and nonresponders could be found in terms of the severity of coronary arterial disease, severity of anginal symptoms, exercise tolerance, antianginal medication, number of past myocardial infarctions, and left ventricular ejection fraction. In conclusion, the data strongly suggest that ischaemic responses to dipyridamole originate from myocardial steal accentuated by compromised flow in collateral vessels.     

Does periodontitis cause heart disease?

See doi:10.1016/j.ehj.2003.09.016and doi:10.1016/j.ehj.2003.10.007forthe articles to which this editorial refers Several studies investigating the relation between infections—includingdental infections—and various clinical manifestationsof atherosclerotic vessel disease have been published duringthe last decade. The topic has proved difficult to study andthis is especially true for dental infections, as they shareseveral common etiologic factors with e.g. coronary heart disease(CHD). These include smoking,     

Pacemaker infections--treatment with total or partial pacemaker system removal

During the years 1977 to 1983, 1,458 pacemakers were implanted or reimplanted in our clinic. Seventy-nine patients were treated during the same period for pacemaker system infections. The time interval between the preceding surgical maneuver and the manifest infection was 11.9 +/- 10.2 months in the catheter fistulas and 12.2 +/- 11.5 months in the pacemaker pocket infections. Forty-one of 79 infections (52%) occurred following the first generator implantation. In 33/43 (76.7%) patients with partial pacemaker system removal, recurrent infection occurred 19.6 +/- 17.2 months later. The infection was treated with similar surgical maneuvers resulting in subsequent infections in 9 patients after 9.8 +/- 7.2 months. In the patients with total pacemaker system removal infection developed in 2/25 (8%). The infection resulted in septicemia in 9 patients. Major surgical intervention was necessary for removal of the infected endocardial electrode in 7 patients. According to our experience there are no grounds for partial removal of the pacemaker system if infection occurs. The primary results may be satisfactory but re-infection will appear in the majority of the patients after a period of several months.