Candida albicans and Candida tropicalis in Oral Candidosis: Quantitative Analysis, Exoenzyme Activity, and Antifungal Drug Sensitivity

Candida albicans and C. tropicalis obtained from whole saliva of patients presenting signs of oral candidosis were assayed for quantification of colony forming units, exoenzyme activity (phospholipase and proteinase) and antifungal drug sensitivity (amphotericin B, fluconazole and itraconazole) by the reference method of the Clinical and Laboratory Standards Institute. The number of colony forming units per milliliter varied according to the Candida species involved and whether a single or mixed infection was present. Proteinase activity was observed in both C. albicans and C. tropicalis, but phospholipase activity was noted only in C. albicans. In vitro resistance to antifungals was verified in both species, but C. tropicalis appears to be more resistant to the tested antifungals than C. albicans.

Computer-aided Drug Design of Novel PLA(2) Inhibitor Candidates for Treatment of Snakebite

Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine its active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.

Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients

Purpose This study investigated the influence of gestational diabetes mellitus on the kinetic disposition and stereoselective metabolism of labetalol administered intravenously or orally. Methods Thirty hypertensive women during the last trimester of pregnancy were divided into four groups: non-diabetic and diabetic women treated with intravenous or oral labetalol. Results The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women receiving the drug intravenously. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the beta-blocker (RR) than for the other enantiomers in both diabetic and non-diabetic women. Gestational diabetes mellitus caused changes in the kinetic disposition of the labetalol stereoisomers when administered orally. The AUC values for the less potent adrenoceptor antagonist (SS) and for the alpha-blocking (SR) isomers were higher in diabetic than in non-diabetic pregnant women. Conclusions The approximately 100% higher AUC values obtained for the (SR) isomer in diabetic pregnant women treated with oral labetalol may be of clinical relevance in terms of the alpha-blocking activity of this isomer.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.

Assessment of the percutaneous penetration of cisplatin: The effect of monoolein and the drug skin penetration pathway

It was intended to examine the in vitro penetration of cisplatin (CIS) through porcine skin in the presence of different concentrations of monoolein (MO) as well as to verify the main barrier for CIS skin penetration. In vitro skin penetration of CIS was studied from propylene glycol (PG) solutions containing 0%, 5%, 10%, and 20% of MO using Franz-type diffusion cell and porcine ear skin. Pretreatment experiments with MO and experiments with skin without stratum corneum (SC) were also carried out. Skin penetration studies of CIS showed that the presence of MO doubled the drug permeation through the intact skin. However, permeation studies through the skin without SC caused only a small enhancement of CIS permeation compared to intact skin. Moreover, pretreatment of skin with MO formulations did not show any significant increase in the flux of the drug. In conclusion, MO did not act as a real penetration enhancer for CIS, but it increased the drug partition to the receptor solution improving CIS transdermal permeation. The absence of improvement in drug permeation by MO pretreatment and by the removal of SC indicates that the SC is not the main barrier for the permeation of the metal coordination compound. (c) 2009 Elsevier B.V. All rights reserved.

Analysis of Liquid Crystalline Nanoparticles by Small Angle X-Ray Diffraction: Evaluation of Drug and Pharmaceutical Additives Influence on the Internal Structure

The goal of this work was to study the liquid crystalline structure of a nanodispersion delivery system intended to be used in photodynamic therapy after loading with photosensitizers (PSs) and additives such as preservatives and thickening polymers. Polarized light microscopy and light scattering were performed on a standard nanodispersion in order to determine the anisotropy of the liquid crystalline structure and the mean diameter of the nanoparticles, respectively. Small angle X-ray diffraction (SAXRD) was used to verify the influence of drug loading and additives on the liquid crystalline structure of the nanodispersions. The samples, before and after the addition of PSs and additives, were stable over 90 days, as verified by dynamic light scattering. SAXRD revealed that despite the alteration observed in some of the samples analyzed in the presence of photosensitizing drugs and additives, the hexagonal phase still remained in the crystalline phase. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2849-2857, 2011

UQ eSpace Users - Frequently Asked Questions

A FAQ on how to use the UQ eSpace repository.

Review of diagnostic screening instruments for alcohol and other drug use and other psychiatric disorders

In recent years there has been a growing recognition that many people with drug or alcohol problems are also experiencing a range of other psychiatric and psychological problems. The presence of concurrent psychiatric or psychological problems is likely to impact on the success of treatment services. These problems vary greatly, from undetected major psychiatric illnesses that meet internationally accepted diagnostic criteria such as those outlined in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association (1994), to less defined feelings of low mood and anxiety that do not meet diagnostic criteria but nevertheless impact on an individual’s sense of wellbeing and affect their quality of life.

The Swiss heroin trials: testing alternative approaches

Over half a million heroin misusers receive oral methadone maintenance treatment world-wide1 but the maintenance prescription of injectable opioid drugs, like heroin, remains controversial. In 1992 Switzerland began a large scale evaluation of heroin and other injectable opiate prescribing that eventually involved 1035 misusers. 2 3 The results of the evaluation have recently been reported.4 These show that it was feasible to provide heroin by intravenous injection at a clinic, up to three times a day, for seven days a week. This was done while maintaining good drug control, good order, client safety, and staff morale. Patients were stabilised on 500 to 600 mg heroin daily without evidence of increasing tolerance. Retention in treatment was 89% at six months and 69% at 18 months.4 The self reported use of non-prescribed heroin fell signifianctly, but other drug use was minimally affected. The death rate was 1% per year, and there were no deaths from overdose among participants . . . [Full text of this article]

Investigation of the antinociceptive efficacy and relative potency of extended duration injectable 3-acylmorphine-6-sulfate prodrugs in rats

This investigation was designed to examine the antinociceptive activity in rats of 3-O-acyl prodrugs of M6S relative to the parent drug, after intravenous and intramuscular injection, using the tail flick latency test of antinociception. M6S, 3-acetylmorphine-6-sulfate (3AcM6S), 3-propionylmorphine-6-sulfate (3PrM6S), 3-butanoylmorphine-6-sulfate (3BuM6S) and 3-heptanoylmorphine-6-sulfate (3HpM6S) were administered by the IV route in a dose of 4.10 mu mol/kg. Relatively high levels of antinociception (>40% Maximum Possible Effect) were achieved following administration of M6S, 3AcM6S and 3PrM6S, whereas insignificant antinociception (<20%MPE) was achieved following administration of 3BuM6S or 3HpM6S. Although the mean duration of action for 3AcM6S (6 h) was longer than for M6S or 3PrM6S (4 h), the mean area (+/- S.E.M.) under the degree of antinociception versus time curve (AUG) for 3AcM6S (151.6 +/- 6.9%MPE h) was not significantly different (p <0.05) from that for M6S (120.8 +/- 32.7%MPE h) or for 3PrM6S (106.0 +/- 21.3%MPE h). The mean ED50 (range) doses for M6S, 3AcM6S and 3PrM6S were calculated to be 4.16 (3.61-4.48), 4.32 (3.55-5.09) and 4.54 (4.21-4.79) mu mol/kg, respectively. Preliminary studies were conducted on potential long-acting formulations containing 8 x ED50 doses of M6S and the 3-acetyl and 3-propionyl esters suspended in soybean oil. These showed that 3PrM6S gave a greater AUC (mean + S.E.M.) (1087.4 +/- 97.4%MPE h) and longer duration of action (20 h) than did M6S (613.1 +/- 155.9%MPE h; 10 h duration) or 3AcM6S (379.3 + 114.2%MPE h: 8 h duration). Further studies are needed to more fully investigate these findings. (C) 1998 Elsevier Science B.V. All rights reserved.

Methadone maintenance and drug-related crime

Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement irt crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped, promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic teas associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. it is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.

Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats

Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G's pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative apparent levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9-5.4 mu mol) dosing or i.p. morphine (10 mu mol) dosing, high levels of antinociception (>50% MPE) were achieved using the tail flick test whereas base-line levels of antinociception were observed 30 sec later in the same rats using the hotplate test. By contrast, antinociception evoked by i.v. morphine (10 mu mol) exceeded 50% MPE using both the hotplate and tail flick tests although the apparent potency was approximately 2.5 times greater using the tail flick test. After i.c.v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. Taken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine's antinociceptive effects.