Effects of β-cyclodextrin and di-O-methyl-β-cyclodextrin on the percutaneous absorption of butylparaben,indomethacin and sulfanilic acid

The effects of β-cyclodextrin (β-CD) and di-O-methyl-β-cyclodextrin (DM-β-CD) on the percutaneous absorption of butylparaben (BP), indomethacin (IM), and sulfanilic acid (SA) were investigated. The flow-through type diffusion cell was used for in vitro penetration experiments. All of the recorded data were fitted to the diffusion equation describing the drug penetration through a homogeneous plane membrane by the non-linear least-squares computer program, and two parameters corresponding to diffusion constant of drug and partition coefficient of that between skin and vehicle were obtained. Both cyclodextrins (CDs) decreased the penetration of BP depending on their concentrations. The decrease in BP penetration was explained by that in calculated apparent partition coefficient of BP and good correlation was observed between the partition coefficient and free BP fraction estimated based on the complex formation stoichiometry. IM penetration was also decreased by complex formation but some additional effects, somewhat different between β-CD and DM-β-CD, were observed. On the contrary, the penetration of SA which scarcely formed complex with either CD was significantly enhanced by DM-β-CD. This was attributed to the effect of DM-β-CD on the skin to reduce its barrier function.     

The influence of physicochemical properties on the reactivity and stability of acyl glucuronides†

1.?Formation of 1-O-acyl-β-d-glucuronide conjugates is a significant pathway in the metabolism of drugs containing a carboxylic acid group. The formation of acyl glucuronides results in an increase in both the aqueous solubility and molecular mass of the conjugate in comparison to the parent drug and thus facilitates excretion in both urine and bile.

2.?Acyl glucuronides are effectively esters, which undergo first order decomposition by both hydrolysis and the intra-migration of the acyl group around the glucuronide ring to yield 2-, 3- and 4-O-glucuronic acid esters which, unlike the metabolically formed 1-O-acyl-β-d-glucuronides, are not substrates for β-glucuronidase. The first order degradation half-life is therefore a composite value of these two reactions and a useful indicator of chemical reactivity and potential toxicity.

3.?Intra-molecular migration is expected to be the predominant pathway due to entropic considerations.

4.?Such conjugates, together with their isomeric ester derivatives, react with nucleophilic sites on proteins and small endogenous molecules, such as glutathione, which potentially contributes to the observed toxicity and adverse drug reactions associated with some drugs.

5.?Examination of the stability of the 1-O-acyl-β-d-glucuronides of aryl acetic acid, α-carbon substituted aryl acetic acid, aliphatic and aromatic acids, as determined by their first order degradation half-lives, indicates the significance of electronic and steric features that contribute to conjugate stability under physiological conditions.

6.?Examination of the of the electronic properties of the carbonyl carbon atom in acyl glucuronides, as measured by the pKa of the parent acid, together with the steric substituents about the acyl carbonyl provides insight into the reactivity of these conjugates.

7.?The investigations reported herein on a large number of 1-O-acyl-β-d-glucuronides has allowed rationalisation of their physicochemical properties in relation to the structure of the parent drug and has the potential to contribute to the design of carboxylic acid containing drug molecules with increased stability of a major metabolite with potential reduction in toxicity and adverse drug reactions.     

The influence of tumour necrosis factor-α on the cardiovascular system of anaesthetized rats

The effects of two vasoactive agents (adenosine A2A agonist, CGS 21680, and adrenoceptor agonist, noradrenaline) were examined on cardiac output (CO), heart rate (HR), blood pressure (BP), mean circulatory filling pressure (Pmcf), resistance to venous return, arterial resistance, dP/dt, plasma levels of NO2-/NO3-, and inducible nitric oxide synthase (iNOS) activity in lungs ex vivo, following treatment with tumour necrosis factor-alpha (TNF-alpha; 30 microg/kg) in anaesthetized rats. Treatment with TNF-alpha produced significant reduction in CO (41+/-2%), dP/dt (26+/-3%), BP (26+/-2%) and Pmcf (27+/-4%; n=6; mean+/-SEM), but increased arterial resistance. There were no significant changes in the plasma levels of NO2-/NO3-levels over time following treatment with TNF-alpha, but there was a significant increase (approximately twofold) in the activity of the iNOS in the lungs of animals treated with TNF-alpha. Administration of CGS 21680 (1.0 microg/kg per min) significantly increased CO (44+/-6%), HR (12+/-2%), Pmcf (24+/-4%) and dP/dt (24+/-5%) in TNF-alpha-treated rats. CGS 21680 also significantly reduced arterial resistance (33+/-2%) without altering resistance to venous return in TNF-alpha-treated rats. While noradrenaline (1.0 microg/kg per min) infusion did not significantly increase CO, it did significantly increase HR (12+/-1%), BP (55+/-9%), Pmcf (47+/-5%), dP/dt (65+/-7%), resistance to venous return (64+/-20%), and arterial resistance (41+/-16%) in TNF-alpha-treated animals. The reduction in BP due to administration of TNF-alpha is the result of significant reduction in CO. Consequently, the decline in CO can be attributed to a combination of a negative inotropic effect as well as a reduction in Pmcf. It is evident that infusion with CGS 21680 could reverse the negative impact of TNF-alpha on CO by increasing dP/dt, Pmcf and HR as well as a reduction in arterial resistance. The fact that noradrenaline did not significantly increase CO in TNF-alpha-treated rats can be attributed to increased arterial resistance as well increase in resistance to venous return.     

The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

The work aims to prove the complexation of two model drugs (ibuprofen, IB and indomethacin, IN) by β-cyclodextrin (βCD), and the effect of water in such a process, and makes a comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug, βCD, and inclusion of either IB or IN in aqueous solutions of βCD. In the latter method water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products, optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-ray and NMR were considered. Each powder was added to an acidic solution (pH = 2) to quantify the concentration of the drug inside βCD cavity. Other media (pH = 5 and 7) were used to prove the existence of drug not complexed in each powder, as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the βCD did not depend neither on the method of complexation nor on the processes of drying considered.     

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

Purpose: The aim of this study was to evaluate a candidate haemostat (WoundStat?), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model.

Materials and methods: An area of approximately 3?cm² was dermatomed from the dorsal ear skin to a nominal depth of 100?µm. A discrete droplet of ¹⁴C-GD (300?µg kg^?1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2?g application of WoundStat? 30?s after GD challenge. The decontamination efficacy of WoundStat? against GD was measured by the direct quantification of the distribution of ¹⁴C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements.

Results: WoundStat? sequestered approximately 70% of the applied ¹⁴C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15?min post WoundStat? treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat? treated animals survived the study duration.

Conclusions: The current study has shown that the use of WoundStat? as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat? in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.     

The influence of molecular structure on the affinity and efficacy of some β-adrenoceptor agonists

Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective ₁-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK _D) was calculated from their ability to displace the radioligand [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) from -adrenoceptor sites in left atrial (₁) and uterine (₂) membrane homogenates. These pK _D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD₂ values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [¹²⁵I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for ₁- and reduces affinity for ₂-adrenoceptors. With this amine group, efficacy is markedly reduced at ₂- as opposed to ₂-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for ₁- as opposed to ₂-adrenoceptors.     

The influence of glutathione on the photoreaction of 3,4′,5-tribromosalicyl-anilide alone and in the presence of serum albumin

Glutathione is known to play a prominent detoxifying role in the organism. In this study attention has been paid to the possible occurrence of a detoxifying action of glutathione in the skin. For this reason we studied the influence of glutathione on the photoreaction of 3,4′,5-tribromosalicylanilide (Tbsa), which is notorious for causing photoallergy. It was found thatTbsa forms stable photoconjugates on irradiation with glutathione: 3-glutathyl-4′,5-dibromosalicylanilide and 5-glutathyl-4′-bromosalicylanilide. The rate of the photoreaction ofTbsa in the presence of glutathione, resulting in photostable products, is increased. Furthermore, covalent binding with serum albumin appeared to be decreased in the presence of glutathione.     

Spectroscopic investigation on the food components–drug interaction: The influence of flavonoids on the affinity of nifedipine to human serum albumin

Nifedipine (NDP) is used extensively for the clinical treatment of a number of cardiovascular diseases. Herein, the interaction between human serum albumin (HSA) and NDP and the influence of flavonoids, rutin and baicalin, on their binding properties were investigated in vitro by means of fluorescence and absorption spectroscopy. The fluorescence of HSA was quenched remarkably by NDP and the quenching mechanism was considered as static quenching by forming a complex. The results of thermodynamic parameters indicate that both hydrogen bonds and hydrophobic interactions play the main role in the binding process and the binding process was spontaneous. The binding distance between the amino acid residue of HSA and NDP is 2.608 nm, which indicates that the energy transfer from HSA to NDP can occur with high probability. The decreased association constants and the increased binding distance of NDP binding to HSA in the presence of flavonoids were both due to their competitive binding to the site I of HSA. The results obtained from synchronous fluorescence and three-dimensional fluorescence spectra showed that the interaction between HSA and NDP caused the conformational changes of HSA and the synergism effects of NDP and flavonoids induced the further conformational changes of HSA.     

The influence of hyperthyroidism on β-adrenoceptor-mediated relaxation of isolated small mesenteric arteries

We investigated the influence of hyperthyroidism on relaxant responses of small mesenteric resistance arteries to -adrenoceptor agonists and to compounds stimulating the corresponding second-messenger system. Hyperthyroidism was induced by feeding rats for 28 days with 5 mg/kg L-thyroxine (T4)-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by several biochemical/metabolic and haemodynamic parameters. Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for isoproterenol, noradrenaline and salbutamol as well as for forskolin, dibutyryl-cAMP and theophylline. We also determined concentration-effect curves to the -adrenoceptor agonists in the presence of ICI 118,551 and CGP 20712A (i.e., in the presence of a selective ₂- and ₁-adrenoceptor antagonist, respectively). Apparent pA₂-values were calculated to determine which -adrenoceptor subtype causes vasodilation. These experiments indicate that -adrenoceptor-mediated vasodilation involves both ₁- and ₂-adrenoceptors in mesenteric resistance vessels of both hyperthyroid and control rats. In our experiments hyperthyroidism has a sensitizing influence on vascular responses induced by the -adrenoceptor agonist isoproterenol and the selective ₂-adrenoceptor agonist salbutamol. Sensitization to isoproterenol was abolished in the presence of ICI 118,551, whereas it was emphasized in the presence of CGP 20712A. Although this was not fully supported by the results obtained with noradrenaline, these results indicate that the sensitization to -adrenoceptor agonists is probably limited to the ₂-adrenoceptor/G-protein complex and not associated with alterations of the corresponding second messenger system.     

The role of surface functionality of sustainable mesoporous materials Starbon® on the adsorption of toxic ammonia and sulphur gasses

The interest in adsorbing toxic gases nowadays is primarily due to their short- and long-term adverse health effects. It is generally accepted that the pore morphology and the surface nature play key roles in the adsorption mechanism of any molecules. The interactions between the adsorbate and adsorbent are affected by their polarity, where nonpolar surfaces would be attracted to a non-polar adsorbate, while polar surfaces have a higher affinity for polar molecules. The primary issue is access to a controllable set of materials with multiple functionalities that provide both polar and nonpolar surfaces for adsorption, which would present an advantage over single-phase adsorbents. Recently this has become available thanks to a novel class of bio-based carbonaceous materials (Starbon®). The functionality of these materials can be easily controlled by their temperature of preparation. The present work studies the nature of the surface chemistry and porosity of bio-based mesoporous materials Starbon and the role this plays in the adsorption of toxic volatile molecules such as ammonia, as a basic adsorptive and two acidic gasses (hydrogen sulphide and sulphur dioxide) using an InfraSorp optical calorimeter. Both hydrogen sulphide and sulphur dioxide adsorb better onto a hydrophobic surface, while ammonia adsorbs best onto a hydrophilic surface. The results showed that in both cases, Starbon significantly outperformed the industrially available powdered Norit® activated carbon (AC) and reacted chemically with the gasses to some extent.     

The influence of inhibition of catechol-O-methyl transferase or of monoamine oxidase on the extraneuronal metabolism of 3H-(−)-noradrenaline in the rat heart

Summary The extraneuronal metabolism of ³H-(–)-noradrenaline (1 nmol/l) was determined in rat hearts obtained from reserpine-pretreated animals (in the presence of 30 mol/l cocaine).Inhibition of monoamine oxidase (MAO) (by pretreatment of the animals with pargyline) increased the formation of O-methylated metabolites by nearly that amount by which the formation of deaminated metabolites declined; hence, catechol-O-methyl transferase (COMT) seemed to be able to nearly fully compensate for the loss of MAO activity. However, when COMT was inhibited (by the presence of either 1 or 10 mol/l U-O521), the increase in the formation of deaminated metabolites was smaller than the decrease in the formation of O-methylated metabolites; hence, MAO seemed to be unable to fully compensate for the loss of COMT activity.These results are discussed with regard to the hypothesis that the two extraneuronal enzymes co-exist in one compartment. As inhibition of COMT causes a much greater increase in the steady-state tissue/medium ratio for ³H-(–)-noradrenaline than does inhibition of MAO, it is suggested that it is this increase in the intracellular concentration of ³H-(–)-noradrenaline which-by promoting an efflux of the unchanged amine that is proportional to the tissue/medium ratio-actually decreases the net removal of ³H-(–)-noradrenaline from the perfusion fluid.The results are compatible with (but no evidence for) the hypothesis that the two enzymes co-exist in the same extraneuronal compartment.The following abbreviations are used here NMN normetanephrine - DOPEG dihydroxyphenylglycol - DOMA dihydroxymandelic acid - MOPEG methoxyhydroxyphenylglycol - VMA methoxyhydroxymandelic acid - OMDA MOPEG+VMA Supported by the Deutsche Forschungsgemeinschaft     

The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood–brain barrier in sheep

Background and purpose:

The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood–brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied.

Experimental approach:

Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg·kg⁻¹, was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K_p,uu) and unbound drug volume of distribution in brain (V_u,brain) were estimated.

Key results:

Morphine K_p,uu was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V_u,brain measurements were higher in sheep than in premature lambs. The M3G K_p,uu values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups.

Conclusions and implications:

The morphine K_p,uu was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.     

Aging influence on regional homogeneity of the motor network in the resting state

Objective： To investigate the influence of aging on regional homogeneity of the motor network in the resting state. Background： Normal aging is accompanied by progressive slowness and impairedmotor ability. However, our knowledge about aging modulation of the central motor system remains sparse and contradictory. In the current study, we used functional MRI （fMRI） to study the aging influence on regional homogeneity of the motor network in the resting state. In addition, a functional connectivity analysis was applied to investigate whether the changed regional homogeneity modulates the function of motor network. Methods： FMRIs were acquired in 12 healthy young and 12 aged subjects during resting state.     

Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler—a Case Study on Aerolizer® Foradile®

The objective of this study is to investigate the effect of device design of the Aerolizer^® on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile^®). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle–device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle–device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer^® were found to impact significantly on the aerosolization of the carrier-based powder.     

Effects of pinacidil on cerebral and mesenteric arteries —influence of the endothelium

Summary The effect of pinacidil on the contractile response to stepwise increases of the extracellular K⁺ concentration ([K⁺]₀) was investigated in isolated segments of human pial and mesenteric arteries and rabbit basilar and mesenteric arteries. The [K⁺]_O eliciting half maximum contraction (EC₅₀) was lower in human pial (18 mM) and rabbit basilar (27 mM) arteries than in human (33 mM) and rabbit (32 mM) mesenteric arteries, respectively. The -adrenoceptor blocker, prazosin, increased the EC₅₀ value for K⁺ from 27 to 40 mM and reduced the maximum response in rabbit mesenteric arteries, but had no effect on the K⁺-induced contraction in rabbit basilar arteries, indicating a substantial noradrenergic component of the K⁺ response in the former arteries. Removal of the endothelium decreased the EC₅₀ value for K⁺ from 27 to 15 mM in rabbit basilar arteries, whereas the K⁺ sensitivity was unaffected in rabbit mesenteric arteries. Pinacidil shifted the K⁺ concentration-response curve to the right in human and rabbit cerebral and mesenteric arteries. In rabbit basilar arteries, but not in mesenteric arteries, the shift was larger in the absence than in the presence of an intact endothelium. When endothelium-denuded rabbit arteries were compared, the inhibitory effect of pinacidil was larger in basilar than in mesenteric arteries. Thus, pinacidil inhibits K⁺-induced contractions in both cerebral and mesenteric arteries, but appears to act preferentially on endothelium-denuded rabbit basilar arteries. Provided that endothelial damage and depolarization-induced vasoconstriction are of pathophysiological importance in cerebrovascular disorders such as stroke and cerebral ischemia secondary to vasospasm after subarachnoid hemorrhage, pinacidil may have a therapeutic potential. Correspondence to E. D. Hogestatt at the above address     

The influence of intervention complexity on barriers and facilitators in the implementation of professional pharmacy services – A systematic review

BackgroundCommunity pharmacies increasingly offer professional pharmacy services, whose implementation is often influenced by facilitating or obstructive implementation factors. The occurrence and composition of implementation factors vary among different services with discrete characteristics and complexity of the intervention, making it difficult to foresee potential barriers in implementation.Objective(s): This paper investigates potential associations between intervention complexity and occurring implementation factors.MethodsA systematic literature search on the implementation factors and intervention complexity of professional pharmacy services in the community setting was carried out in electronic databases (PubMed, CINAHL, and PsycINFO) throughout December 2018. Implementation factors were extracted from semi-structured interviews, focus groups, and surveys with community pharmacists and categorized using the Consolidated Framework for Implementation Research (CFIR). The complexity of each service was assessed using the following complexity parameters: (I) number of involved healthcare professions, (II) number of service components such as recruiting of patients, screening intervention, and follow-up, (III) frequency of the service, (IV) expenditure of time per patient (encounter), and (V) workflow distortion, i.e. booking appointments for intervention with the patient. Finally, the association between implementation factors and intervention complexity was analyzed by quantifying implementation factors and by relating them to specific intervention characteristics using Fisher's exact test.Results15 studies covering a broad spectrum of professional pharmacy services were included. There was a trend that in services with higher complexity more implementation factors occurred (p = 0.094). Single key complexity parameters can trigger specific implementation factors. For instance, general practitioner and pharmacy technician involvement were significantly associated with interprofessional communication and leadership engagement, respectively.ConclusionKey implementation factors and associated complexity parameters seem to be of similar or more importance than the total number of implementation factors with regard to successful implementation. By assessing various complexity parameters of an intervention, potential key barriers could be identified and subsequently addressed prior to implementation.     

The effect of FT500 Plus® on ovarian stimulation in PCOS women

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus^®). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1 ± 0.9 versus 13.5 ± 1; P = 0.0001). Group A showed a significant increase in the number of MII oocytes (6.3 ± 2.5 versus 4.5 ± 2; P = 0.03) and glutathione peroxidase activity in follicular fluid (15.4 ± 6.2 versus 11 ± 2.2; P = 0.04). FT500 Plus^® may be considered in PCOS patient for improving oocyte quality.     

The drug delivery and biomaterial attributes of the ATRIGEL®technology in the treatment of periodontal disease

Two new products, ATRIDOXΟχιρχPeriodontal Treatment and ATRISORB^® Guided Tissue Regeneration (GTR) Barrier have been evaluated as therapies for periodontal disease. Both products are based on the unique ATRIGEL^® technology. The system consists of a solution of a resorbable polymer in a biocompatible carrier. On in vivo administration, the polymer undergoes a phase change from a liquid to an in situ formed implant. Being in liquid form, it initially provides the advantage of in vivo placement by simple means, such as syringes to form implants at the site of use. The system is biocompatible and has the capability of serving as a biomaterial and a drug delivery system. The bioabsorption rates of various polymers and the release rates for a wide variety of drugs ranging from simple organics to proteins and peptides are tailored to the desired indication. Release periods ranging from one week to four months have been achieved with one month being the most often desired. For these reasons the ATRIGEL^Ογρα?ε system is being applied to a number of medical applications ranging from site and systemic oncology to post-operative pain control and bone regeneration using growth factors. However, its most visible application to date has been in the development of a pipeline of products for the treatment of periodontal disease, which is the focus of this paper.