The potential beneficial role of isoflavones in type 2 diabetes mellitus.

Diabetes is a chronic global disease afflicting a substantial number of people worldwide. Different mechanisms have been highlighted in the progression of this disease such as dysfunction of pancreatic ß-cells, insulin resistance, elevated levels of free fatty acids which result in overproduction of reactive oxygen species, as well as pancreatic ß-cell failure and apoptosis. Isoflavones, are polyphenolic phytochemicals found in most leguminous plants, and have been identified as potentially useful antidiabetic agents. The pleiotropic effects of isoflavones include the targeting of numerous cell signaling pathways involved in the pathogenesis of diabetes. Several observational studies have supported the direct relationship between isoflavones intake and a lowered risk of diabetes. The aim of this review was to summarize relevant findings on the effects of isoflavone intake and risk of type II diabetes mellitus (T2DM), and to highlight some of the possible anti-diabetic molecular mechanisms of these polyphenols. Despite the promising therapeutic effects of isoflavones to moderate risk of T2DM, the underlying mechanisms for their preventive effects are still largely unknown. The acceptable human dosage levels of these polyphenols remain a debatable topic as these have a profound influence on the observed benefits. Considerable numbers of well-controlled, long-term human clinical studies of these phytochemicals are highly recommended. Furthermore, combinations of isoflavones and their derivatives in combination with other naturally isolated compounds, and perhaps even those drugs currently used therapeutically to control diabetes mellitus in clinical practice, may be worth exploring in the future.

Dietary supplements containing prohibited substances.

Dietary supplement use among athletes to enhance performance is proliferating as more individuals strive for obtaining that chemical competitive edge. As a result the concomitant use of dietary supplements containing performance-enhancing substances of those falling in the categories outlined in the current review, can also be expected to rise. This despite ever-increasing sophisticated analytical methodology techniques being used to assay dietary supplement and urine samples in doping laboratories. The reasons for this include that a variety of these chemical entities, many of them on the prohibited drug list of the WADA, are being produced on commercial scales in factories around the world (ephedrine and pseudoephedrine, sibutramine, methylhexaneamine, prohormones, 'classic' anabolic steroids, clenbuterol, peptide hormones etc.), aggressive marketing strategies are being employed by companies and these supplements can be easily ordered via e.g. the internet. It can also be anticipated that there will be an increase in the number of supplements containing 'designer' steroids and other 'newer' molecules. Chromatographic techniques combined with mass spectrometry leading to identification of molecular fragments and productions will assist in determining these substances. To prevent accidental doping, information regarding dietary supplements must be provided to athletes, coaches and sports doctors at all levels of competition. The risks of accidental doping via dietary supplement ingestion can be minimized by using 'safe' products listed on databases, e.g. such as those available in The Netherlands and Germany.

The effect of betel nut extract on cell growth and prostaglandin endoperoxide synthase in human epidermoid carcinoma cells.

The objective of this study was to find out whether prostaglandin endoperoxide synthase (PHS) involves the action of betel nut extract (BNE) on the growth of oral cancers. Therefore, growth and PHS activity were examined in two human oral carcinoma cell lines (OEC-M1 and KB) and one normal fibroblast cell line (NF) in the presence of increasing BNE concentration. BNE at concentrations above 50 microg/ml significantly inhibited the cell growth of OEC-M1 after 72 h in culture, of KB and NF after 48 h in culture. The IC50 of BNE in OEC-M1, KB and NF at 24 h in culture was about 406, 37.5 and 140 microg/ml respectively. PHS activity in OEC-M1 was significantly increased by low BNE concentrations (50 microg/ml, 114%; 100 microg/ml, 33%; 150 microg/ml, 30%) but significantly reduced at higher BNE concentrations (300 microg/ml, 33%; 500 microg/ml, 61%). The PHS activity in KB was significantly inhibited by BNE and this effect was intensified as concentrations increased (50 microg/ml, 31%; 100 microg/ml, 24%; 150 microg/ml, 43%; 300 microg/ml, 60%; 500 microg/ml, 92%). Similar to that in OEC-M1, the PHS activity in NF was significantly increased at low BNE concentrations (50 microg/ml, 139%; 100 microg/ml, 87%;150 microg/ml, 77%) but reduced at higher concentrations (300 microg/ml, 55%; 500 microg/ml, 72%). The PHS activity in all cell lines was almost completely blocked by indomethacin (5 x 10(-6) M). We conclude that these findings suggest that PHS may be an important biochemical mediator of the effect of BNE on the growth of two human oral carcinoma cell lines.

Areca nut extract lowers the permeability of vaginal mucosa to reduced arecoline and arecaidine.

Areca nut chewing has been implicated in the development of oral cancer and oral submucous fibrosis. Arecoline and arecaidine, which are alkaloids present in the areca nut, are thought to play a major role in the development of adverse effects resulting from this chewing habit. Because these alkaloids appear to be associated with the development of the above diseases, we determined their diffusion kinetics through human vaginal mucosa in the presence and absence of a 1% areca nut extract. Seven clinically healthy vaginal mucosa specimens (mean patient age+/-standard deviation, 52+/-13 years; age range, 38-74 years) were obtained during surgery. In vitro flux values of reduced arecoline and arecaidine (r-arecoline and r-arecaidine) were determined through use of a flow-through diffusion apparatus. Analysis of variance, a Duncan multiple range test, and an unpaired t-test were used to determine steady state kinetics and flux differences over time intervals. The flux values across vaginal mucosa of r-arecoline and r-arecaidine were decreased in the presence of 1% areca nut extract. For r-arecoline, these flux values were significantly lower statistically when compared to those obtained in the absence of areca nut extract. These findings concur with results previously obtained for water, where the astringent action of the tannins present in the areca nut extract was thought to alter the barrier properties of the epithelium, resulting in decreased permeability.

Prolonged diplopia following a mandibular block injection.

A case is presented in which a 14-yr-old girl developed diplopia after injection of the local anesthetic Xylotox E 80 A (2% lidocaine with 1:80,000 epinephrine). Since the complication had a relatively slow onset and lasted for 24 hr, the commonly suggested explanations based on vascular, lymphatic, and neural route theories do not adequately fit the observations. No treatment, other than reassurance, was necessary, and the patient recovered fully.

Synthesis of non-hydroxy-galactosylceramides and galactosyldiglycerides by hydroxy-ceramide galactosyltransferase.

Galactosylceramide (GalCer) is the major glycolipid in brain. In order to characterize the activity of brain UDPgalactose: ceramide galactosyltransferase (CGalT), it has been stably expressed in CGalT-negative Chinese hamster ovary (CHO) cells. After fractionation of transfected cells, CHO-CGT, on sucrose gradients, the activity resides at the density of endoplasmic reticulum and not of Golgi. A lipid chromatogram from CHO-CGT cells revealed two new iodine-staining spots identified as GalCer, since they comigrate with GalCer standards, can be metabolically labelled with [3H]galactose, are recognized by anti-GalCer antibodies, and are resistant to alkaline hydrolysis. A third [3H]galactose lipid was identified as galactosyldiglyceride. In the homogenate CGalT displays a 25-fold preference for hydroxy fatty acid-containing ceramides. Remarkably, endogenous GalCer of transfected cells contains exclusively non-hydroxy fatty acids: fast atom bombardment and collision-induced dissociation mass spectrometric analysis revealed mainly C16:0 in the lower GalCer band on TLC and mainly C22:0 and C24:0 in the upper band. Our results suggest that CGalT galactosylates both hydroxy- and non-hydroxy fatty acid-containing ceramides and diglycerides, depending on their local availability. Thus, CGalT alone may be responsible for the synthesis of hydroxy- and non-hydroxy-GalCer, and galactosyldiglyceride in myelin.

Rigidity of dental local anaesthetic injection needles.

The objective of this study was to determine the rigidity of 11 different types (4 brands) of dental local anaesthetic injection needles available in South Africa. Twenty needles of each type were attached to a Zwick material testing apparatus and subjected to pressure testing. Stress vs deformation curves were obtained for each needle. The data obtained was logarithmically converted and subjected to an analysis of covariance. The results from this study showed that there were statistically significant differences in the rigidity of dental needles available on the South African market.

The effect of baked areca nut extract on the growth of buccal mucosa fibroblasts from healthy non-areca nut chewers.

Oral submucous fibrosis is a serious oral disease associated with the habit of chewing areca nut. The habit is relatively common among South Africans of Indian descent. The aim of this study was to observe the effect on growth of buccal mucosa fibroblasts derived from healthy individuals not practising the areca nut habit when the cells are exposed to nut extract. Fibroblast cell-lines from 6 individuals were grown in medium without extract and medium containing 50 and 100 [symbol: see text] g/ml extract of baked nut for 8 days. Cells not exposed to the nut extract behaved homogeneously. Reaction to the nut extracts, however, was dissimilar. The cells of 5 individuals showed no discernable reaction to the extracts while in one instance, the cells of a healthy adult male with no physical disabilities, showed marked growth inhibition. Thus, the finding indicates that when the effect of the nut or its constituents are tested on cells, it is necessary to use several cell-lines of the same cell type or a cell-line of which the growth parameters are standardized.

Injection needles for dental local anesthesia.

The implication of the physical characteristsof single-use disposable dental needles for administration local anesthetics, and the role of these properties in causing breakage, pain on injection, and morbidity in patients are reviewed in this article.

Effect of chilli (Capsicum frutescens) extract on proliferation of oral mucosal fibroblasts.

Various concentrations of chilli extract were tested in 2 stages on the growth of a human buccal mucosa fibroblast cell line. Firstly, concentrations of 25, 75, 150 and 300 micrograms/ml were tested on the cell line for 6 days followed by a repeat which included concentrations of 400 and 500 micrograms/ml. In the latter, cell growth was monitored for 18 days. From day 3 (72 hr) suppression of cell growth was evident with concentrations 300-500 micrograms/ml. Total cell death occurred at 16 days with 300 micrograms/ml and at 6 days with 400-500 micrograms/ml. With the lower concentrations, 25-150 micrograms/ml, the daily counts were lower than the control but the difference was not statistically significant. Growth continued unabated. It is therefore concluded that cytopathic effect of chilli extract to fibroblasts is concentration dependent.

Failure of dental local anaesthetic cartridges under pressure.

The objective of this study was to determine the pressures that caused cartridge failure (leakage or fracture) of six different dental local anaesthetics available in South Africa. Forty glass cartridges of each local anaesthetic were placed in an apparatus and subjected to pressure testing using two different plungers. Failure of the cartridges was observed visually as well as on the computer screen of the testing apparatus. In addition the compressibility of local anaesthetic rubber stoppers (bungs) was measured. The data obtained was analysed by means of a two-way analysis of variance and a chi-square test. The results from this study showed that there were statistically significant differences in the mean pressures that caused failure of local anaesthetic cartridges available on the South African market.

Observations on the effect of areca nut extracts on oral fibroblast proliferation.

The effects of aqueous extracts of raw, baked and boiled areca nuts were tested on cultured human buccal mucosa fibroblasts. Cells were exposed to extract concentrations of 0, 50, 100, 150, 300 and 500 micrograms/ml. The arecoline and arecaidine content was determined in the extracts with HPLC and raw nut contained 5.5% m/m, baked nut 6.6% m/m and boiled nut 7.1% m/m. Extract concentrations of 50 to 150 micrograms/ml inhibited cell growth in a concentration-dependent manner but did not lead to total cell death during a 7 day period. However, total cell death did occur with concentrations of 300 and 500 micrograms/ml. It is concluded that areca nut extract is toxic to cultured fibroblasts and inhibits their proliferation in a concentration-dependent manner.

Adverse reactions associated with norepinephrine in dental local anesthesia.

Two cases are presented in which a 40-yr-old woman and a 20-yr-old woman developed severe headaches after injection of the local anesthetic Xylestesin-F (3% lidocaine with 1:25,000 norepinephrine). It is suggested that these severe headaches may have been associated with acute transient hypertensive episodes following injection of the local anesthetic. A review of the literature indicates that norepinephrine, at least at a concentration of 1:25,000, should be avoided because of its potential for cardiovascular disturbances.

Comparison of various physiologic and psychomotor parameters in patients sedated with intravenous lorazepam, diazepam, or midazolam during oral surgery.

Intravenously administered lorazepam (0.05 mg/kg), diazepam (0.25 mg/kg), and midazolam (0.1 mg/kg) were compared for sedation during oral surgery under local anesthesia. Sixty patients were randomly allocated into three groups in this double-blind, parallel study. The results from this trial show that all three drugs provide satisfactory sedation. Average mean arterial pressures, however, decreased significantly with midazolam and diazepam. Statistically significantly higher heart rates during the entire procedure were also found for lorazepam when compared with diazepam and midazolam. At the postblock stage, the midazolam group had respiratory rates that were significantly higher than those of the other two drug groups. Patients in the diazepam and midazolam groups took significantly longer to complete the pegboard test at the preblock stage than those in the lorzepam group. At 1, 1.5, and 2 hours after arrival in the recovery room, an inversion of groups took place, with the lorazepam group taking significantly longer for their tests than the other two groups. Significantly more improvement in anxiety levels was found at 10 minutes postdrug for the patients who had received diazepam and this tended to remain so on arrival in the recovery room. When compared with the other two groups, significantly more patients in the lorazepam group reported giddiness/dizziness and significantly more in the diazepam group reported pain on injection.