Pentacyclic triterpenes from Terminalia arjuna show multiple benefits on aged and dry skin.

BACKGROUND: Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated. METHODS: Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed. RESULTS: Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-ß and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography. CONCLUSION: T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo.

5-Fluorouracil (FU) and mitomycin C (MMC) in the management of colorectal carcinoma. Part II. In vitro activity of the two drugs in short-term tumor cultures.

Eighty-seven colorectal adenocarcinomas from untreated patients were investigated by short term tumor cultures to test in vitro sensitivity to 5-fluorouracil and mitomycin C. This study reports the preliminary results of a multistep program aimed at the prospective clinical application of the assay. At present this in vitro experience was performed in parallel with a clinical trial carried out with the same drugs. The in vitro activity of the two anticancer agents is in agreement with the response rate reported in monochemotherapy; our data would suggest an increase of responses using the combination of fluorouracil and mitomycin in comparison to single drug therapy. A low cosensitivity rate and a high number of cases sensitive to one drug but resistant to the other, account for the use of this test as screening of active drugs in the individual patient.

Pharmacokinetic study on intravenous rifampicin in man.

A pharmacokinetic study was carried out in 18 male patients in order to assess the blood concentrations of rifampicin after intravenous administration of 3 different doses (600, 900 and 1200 mg) over 3 different periods of infusion (1, 2 and 3 hours). The results show that, by increasing the dose and the rate of infusion higher and earlier peak concentrations are obtained. A kinetic analysis based on a one-compartment open model gives a good fitting of the data obtained experimentally. From these data one obtains for the volume of distribution a value of 48.1 +/- 17.2 liters and for the serum disappearance rate the value of 0.212 +/- 0.070 h-1 in adult subjects. It is possible to predict the time course of serum kinetics of the drug by using the equation (formula; see text).

Bioavailability of rifampicin capsules.

In a 3-year bioavailability program 14 studies in 45 healthy volunteers were carried out to differentiate between experimental lots of rifampicin (RMP) capsules and marketed preparations of other manufacturers with lower bioavailability than Rifadin (RFD), used as standard reference drug. In each study single oral doses of 600 mg of 2-5 different RMP preparations were administered to 6-12 volunteers in fasting conditions according to a balanced crossover design. The pharmacokinetic parameters of RFD capsules were practically identical for the same batch tested at different times and for several batches tested in different groups of subjects. Variations in particle size, excipients, or manufacturing process of the experimental preparations or capsules marketed by other manufacturers produced a marked change in bioavailability of RMP. An additional study in four volunteers given 450 mg RMP confirmed that the absorption of RMP is less when the drug is taken with food. It is concluded that due to the wide variability in individual serum levels reported in the literature, some patients who absorb RMP poorly may be given ineffective therapy, especially when there are several concomitant unfavorable factors, such as a poor drug product or the effect of food.

Influence of food intake on the absorption of diftalone in man.

An average 2.2-fold increase in the peak plasma concentrations of the non-steroidal anti-inflammatory agent diftalone in the presence of food was observed in three studies carried out with healthy volunteers who received an oral dose of 0.75 g (6 subjects, study 1), 0.25 g (10 subjects, study II) and 0.5 g (6 subjects, study V) of the compound at 9:00 a.m. both in fasting conditions and after a meal. The effect does not depend on the unusual time (8:00 a.m., selected for experimental needs) at which the subjects were given the meal. In fact, a 2.5-fold increase in plasma concentrations was observed when an oral dose of 0.75 g of diftalone was administered to 2 subjects (study II) both at 8:00 a.m. in fasting conditions and at 1:00 p.m. after a meal. A similar enhancement in the absorption of diftalone was observed when 5 healthy volunteers (study VI) received an oral dose of 0.5 g of the compound both as plain capsules and as capsules containing dry ox bile. However, the absorption of diftalone was not modified when the compound was administered orally as an aqueous suspension or in tensioactive vehicles, or after 20 mg of metoclopramide (study II). Also, the results of a study (IV) on 2 subjects partly deprived of bile after surgery, showed that diftalone does not undergo enterohepatic circulation. The hypothesis that the increase in diftalone absorption is mainly due to bile flow following food intake is supported by all the above experimental results.