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Management of postoperative pain relieve suffering and leads to earlier mobilization, shortened hospital stay, reduced hospital costs, and increased patient satisfaction. An effective postoperative management is not a standardized regime rather is tailored to the needs of the individual patient, taking into account medical, psychological, and physical condition; age; level of fear or anxiety; surgical procedure; personal preference; and response to therapeutic agents given. The major goal in the management of postoperative pain is to minimize the dose of medications to lessen side effects & provide adequate analgesia. Postoperative pain is still under managed due to obstacles in implementation of Acute Pain Services due to insufficient education, fear of complications associated with available analgesic drugs, poor pain assessment and inadequate staff. This review reflects the clinical aspects of postoperative pain & its assessment & management with an emphasis on research for new analgesic molecules & delivery system.

Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous medium using the Pearl Milling technique. The optimized formulation was characterized in terms of particle size distribution, surface morphology, drug-surfactant interaction, drug content, saturation solubility, osmolarity, and stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased saturation solubility as compared to the parent drug. The formulation was found to be iso-osmolar with blood and stable up to 3 months at 2â8ÂC. In-vivo studies were carried out in albino rats and the pharmacokinetic parameters were compared with a marketed formulation, which indicated better results of the prepared formulation than the marketed one.

Tuberculosis has claimed its victims throughout much of known human history and is currently the most devastating human bacterial disease. The ability to infect human population on a global scale, combined with the widespread emergence of multi-drug resistant strains, has led to the placement of Mycobacterium tuberculosis on the National Institute of Allergy and Infectious Diseases (NIAID) list of Biodefence and Emerging Infectious Disease Threats Agents. The resurgence of interest in tuberculosis (TB) has stemmed because of increased evidences from developed countries. Contrary to expectations, no country has reached the phase of elimination and in no subsection of society TB has been completely eliminated. A deeper understanding of the process will assist in the identification of the host and mycobacterial efforts involved and provide targets for therapeutic strategies against tuberculosis. The article presents a view on pathogenesis of tuberculosis and its diverse manifestations, host defense evasion, mechanisms of microbial persistence, emergence of Multiple Drug Resistance and Extensive Drug Resistance, conventional therapy used and the possible novel systems which are under extensive investigation as drug carriers for improving the cytosolic concentration of the anti-tubercular agents.

Nowadays, the recognition of the benefits of antioxidants is eliciting an increasingly interest in the search for new molecules with improved activity. The aim of the present work was to search for improved reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavengers by testing new structures of 2-styrylchromones (2-SC) and 3-substituted flavones, which were synthesised by the Baker-Venkataraman approach. The new compounds were also tested for their metal chelating capacity and reducing activity. The obtained results showed that the methylation of hydroxyl groups decreases the scavenging of ROS and RNS by 2-SC. The decrease in the scavenging activities was, generally, more evident when the methylation occurred in B-ring, except for O2*- and (1)O(2). On the other hand, the introduction of a substituent, either hydroxyl or methoxyl, in position 8 was sometimes favourable and others unfavourable to the scavenging activities, depending on the reactive species. In conclusion, the study of the antioxidant properties of the new 2-SC and flavones allowed establishing new structure-activity relationships and brought out, in some cases, pharmacophores with improved activity.

Protease production was carried out in solid state fermentation. The enzyme was purified through precipitation with ethanol at 72% followed by chromatographies in columns of Sephadex G75 and Sephacryl S100. It was purified 80-fold and exhibited recovery of total activity of 0.4%. SDS-PAGE analysis indicated an estimated molecular mass of 24.5 kDa and the N-terminal sequence of the first 22 residues was APYSGYQCSMQLCLTCALMNCA. Purified protease was only inhibited by EDTA (96.7%) and stimulated by Fe(2+) revealing to be a metalloprotease activated by iron. Optimum pH was 5.5, optimum temperature was 75 degrees C, and it was thermostable at 65 degrees C for 1 h maintaining more than 70% of original activity. Through enzyme kinetic studies, protease better hydrolyzed casein than azocasein. The screening of fluorescence resonance energy transfer (FRET) peptide series derived from Abz-KLXSSKQ-EDDnp revealed that the enzyme exhibited preference for Arg in P(1) (k(cat)/K(m) = 30.1 mM(-1) s(-1)).

Dravet syndrome (also called severe myoclonic epilepsy of infancy) is one of the most severe forms of childhood epilepsy. Most patients have heterozygous mutations in SCN1A, encoding voltage-gated sodium channel Na(v)1.1 alpha subunits. Sodium channels are modulated by beta1 subunits, encoded by SCN1B, a gene also linked to epilepsy. Here we report the first patient with Dravet syndrome associated with a recessive mutation in SCN1B (p.R125C). Biochemical characterization of p.R125C in a heterologous system demonstrated little to no cell surface expression despite normal total cellular expression. This occurred regardless of coexpression of Na(v)1.1 alpha subunits. Because the patient was homozygous for the mutation, these data suggest a functional SCN1B null phenotype. To understand the consequences of the lack of beta1 cell surface expression in vivo, hippocampal slice recordings were performed in Scn1b(-/-) versus Scn1b(+/+) mice. Scn1b(-/-) CA3 neurons fired evoked action potentials with a significantly higher peak voltage and significantly greater amplitude compared with wild type. However, in contrast to the Scn1a(+/-) model of Dravet syndrome, we found no measurable differences in sodium current density in acutely dissociated CA3 hippocampal neurons. Whereas Scn1b(-/-) mice seize spontaneously, the seizure susceptibility of Scn1b(+/-) mice was similar to wild type, suggesting that, like the parents of this patient, one functional SCN1B allele is sufficient for normal control of electrical excitability. We conclude that SCN1B p.R125C is an autosomal recessive cause of Dravet syndrome through functional gene inactivation.

The development of multidrug resistance (due to drug efflux by P-glycoproteins) is a major drawback with the use of paclitaxel (PTX) in the treatment of cancer. The rationale behind this study is to prepare PTX nanoparticles (NPs) for the reversal of multidrug resistance based on the fact that PTX loaded into NPs is not recognized by P-glycoproteins and hence is not effluxed out of the cell. Also, the intracellular penetration of the NPs could be enhanced by anchoring transferrin (Tf) on the PTX-PLGA-NPs. PTX-loaded PLGA NPs (PTX-PLGA-NPs), Pluronic((R))P85-coated PLGA NPs (P85-PTX-PLGA-NPs), and Tf-anchored PLGA NPs (Tf-PTX-PLGA-NPs) were prepared and evaluted for cytotoxicity and intracellular uptake using C6 rat glioma cell line. A significant increase in cytotoxicity was observed in the order of Tf-PTX-PLGA-NPs > P85-PTX-PLGA-NPs > PTX-PLGA-NPs in comparison to drug solution. In vivo biodistribution on male Sprague-Dawley rats bearing C6 glioma (subcutaneous) showed higher tumor PTX concentrations in animals administered with PTX-NPs compared to drug solution.

It is shown that the relationship between the alkyl chain length of 3-alkyl-3',4',5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n=1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu(2+)-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H(2)O(2,) at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity.

Quetiapine fumarate is an atypical antipsychotic with relatively benign side-effect profile. Here we report a rare side-effect of quetiapine use. This is the second reported case of peripheral edema with quetiapine use. Unaware of this rare side-effect, patient had to endure extensive investigations.

Calcium phosphate is considered as a potential biomaterial for drug and gene delivery because of its excellent features. In this study, we reported the formulation and characterization of calcium phosphate nanoparticle containing anticancer drug, methotrexate (MTX). Calcium phosphate nanoparticles containing MTX (CaPi-MTX) were prepared by reverse micelles technique. CaPi-MTX nanoparticles of average size 262 +/- 47.64 nm with entrapment efficiency of 58.04 +/- 4.09% were obtained. The IR spectrum of CaPi-MTX showed characteristics of composite formation of hydroxyapatite with MTX. X-RD analysis revealed that, CaPi-MTX nanoparticles were crystalline and in hydroxyapatite form. TEM studies showed that CaPi-MTX nanoparticles were spherical in shape. In vitro release study of CaPi-MTX nanoparticles showed slow release of MTX at physiological pH (pH 7.4) while > 90% release was observed within 3-4 hours at endosomal pH (pH 5.5 and pH 6.0). Confocal microscopy was performed using CHO cell lines, showed intracellular localization of FITC-Dextran loaded calcium phosphate nanoparticles. Results indicate that prepared CaPi-MTX nanoparticles could serve the purpose for intracellular drug delivery.

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2 +/- 2.58%) with the mean diameter of 220 +/- 6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t(1/2) (28.86 h) and AUC 2526.88 mug/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.

Chronic inflammation with the presence of excess serum acute-phase proteins, cytokines and cell adhesion molecules is increasingly being implicated in atherosclerosis. The association between inflammatory bowel disease (IBD) and coronary artery disease (CAD) is unstudied. This is a preliminary, thesis-generating cross-sectional study aimed at evaluating the presence of traditional atherosclerotic risk factors in patients with IBD and CAD compared with the control population. The medical records of 42 consecutive IBD patients with CAD from 1999 to 2005 (27 men) were reviewed for the Framingham risk factors. The Framingham risk score (FRS) is calculated based on age, sex, hypertension, diabetes and hyperlipidemia. FRS of patients with IBD and CAD was compared with the FRS of 137 age- and sex-matched (102 men) consecutive patients with CAD (controls). When the Framingham risk score adjusted for group and gender with age as a covariate, the adjusted total FRS score was higher in patients with CAD alone (10.0 [3.75]) as compared to those with; IBD and CAD: (8.1 [3.47]; p = 0.001). FRS is lower in cases (patients with IBD and CAD) when compared with the controls (CAD alone).

In micellar solutions, one-electron reduction of *O2(-) radical-anions by 3-alkylpolyhydroxyflavones (FnH) with alkyl chains of n = 1, 4, 6, 10 carbons produces phenoxyl radicals ( (*Fn) identical to those obtained by one-electron oxidation by *Br2(-) radical-anions or by repair of tryptophan radicals. In cetyltrimethylammonium bromide (CTAB), F1H localizes in the Stern layer, and alkyl chains of other FnH solubilize in the hydrophobic interior, interacting with cetyl tails. This interaction produces more compact micelles with lower intramicellar fluidity, as suggested by the increase in the pseudo-first-order rate constant of *Fn formation ( k 1) from approximately 390 s (-1) for n = 1 to 610 s (-1) for n = 10, leading to an intramicellar bimolecular rate constant of 1 x 10 (5) M (-1) s (-1). Additionally, *F1 and *F4 decay by intermicellar bimolecular reaction (2 k = 20 and 2 x 10 (5) M (-1) s (-1), respectively) whereas other *Fn radicals are stable over seconds due to increased localization with regards to the Stern layer. In contrast, the thick uncharged hydrophilic palisade layer and the compact hydrophobic core of Triton X100 micelles are responsible for a much higher microviscosity resulting in a decrease in k 1 from approximately 15.6 s (-1) for n = 1 to 9.6 s (-1) for n = 10.

The purpose of this research was to study the effect of the lipid matrix on the entrapment of olanzapine (OL). OL-loaded solid lipid nanoparticles (SLNs) were prepared using lipids like glyceryl monostearate (GMS), Precirol ATO 5 (PRE), glyceryl tristearate (GTS), and Witepsol E85 (WE 85)--and poloxamer 407 and hydrogenated soya phosphatidylcholine as stabilizers--using a hot melt emulsification high-pressure homogenization technique, and then characterized by particle size analysis, zeta potential, differential scanning calorimetry (DSC), and powder X-ray diffraction (pXRD). Homogenization at 10,000 psi for 3 cycles resulted in the formation of SLNs with a mean particle size of approximately 190 nm for the 4 lipids investigated. The highest partition coefficient for OL between the melted lipid and pH 7.4 phosphate buffer (pH 7.4 PB) was obtained with GTS. The entrapment efficiency was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. DSC and pXRD showed that much of the incorporated fraction of OL existed in the amorphous state after incorporation into SLNs. A sharp increase in the flocculation of the SLN dispersions was observed upon addition of 0.6 M aqueous sodium sulfate solution. Nanoparticle surface hydrophobicity was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. A significant increase in size and zeta potential was observed for GTS SLN and WE 85 SLN dispersions stored at 40 degrees C. Release of OL from the SLNs was sustained up to 48 hours in pH 7.4 PB and obeyed Higuchi's release kinetics.

Extensive efforts have recently been focused on targeting a drug or delivery system in a particular region of the body for extended period of time, not only for local targeting of drugs but also for the better control of systemic drug delivery. The concept of periodontal drug delivery systems has fascinated many investigators to the possible use of various polymers, which can overcome various physiological barriers in long-term drug delivery, there by rendering the treatment more effective and safe for local disorders and systemic problems. Presence of a smooth and relatively immobile surface for placement of a bio-adhesive dosage form has made periodontal route more suitable for sustained delivery of therapeutic agents using bio-adhesive systems. Antibiotics, antiseptics and other poorly absorbable drugs can be successfully delivered via periodontium for the treatment of infectious periodontal diseases. The dosage forms include microparticles, microspheres, adhesive gels, adhesive films, adhesive creams and ointments. Bio-adhesive periodontal drug delivery system can also exert positive influence on drug effectiveness by keeping the drug in the region proximal to its absorption window and allow the targeting and localization of the drug at the specific site.

An extracellular polygalacturonase was isolated from 5-day culture filtrates of Thermoascus aurantiacus CBMAI-756 and purified by gel filtration and ion-exchange chromatography. The enzyme was maximally active at pH 5.5 and 60-65 degrees C. The apparent K (m) with citrus pectin was 1.46 mg/ml and the V (max) was 2433.3 micromol/min/mg. The apparent molecular weight of the enzyme was 30 kDa. The enzyme was 100% stable at 50 degrees C for 1 h and showed a half-life of 10 min at 60 degrees C. Polygalacturonase was stable at pH 5.0-5.5 and maintained 33% of initial activity at pH 9.0. Metal ions, such as Zn(+2), Mn(+2), and Hg(+2), inhibited 50, 75 and 100% of enzyme activity. The purified polygalacturonase was shown to be an endo/exo-enzyme, releasing mono, di and tri-galacturonic acids within 10 min of hydrolysis.

The purpose of this review is to provide an insight into the different aspects of pH-sensitive liposomes. The review consists of 6 parts: the first introduces different types of medications made in liposomal drug delivery to overcome several drawbacks; the second elaborates the development of pH-sensitive liposomes; the third explains diverse mechanisms associated with the endocytosis and the cytosolic delivery of the drugs through pH-sensitive liposomes; the fourth describes the role and importance of pH-sensitive lipid dioleoylphosphatidylethanolamine (DOPE) and research carried on it; the fifth explains successful strategies used so far using the mechanism of pH sensitivity for fusogenic activity; the final part is a compilation of research that has played a significant role in emphasizing the success of pH-sensitive liposomes as an efficient drug delivery system in the treatment of malignant tumours. pH-Sensitive liposomes have been extensively studied in recent years as an amicable alternative to conventional liposomes in effectively targeting and accumulating anti-cancer drugs in tumours. This research suggests that pH-sensitive liposomes are more efficient in delivering anti-cancer drugs than conventional and long-circulating liposomes due to their fusogenic property. Research focused on the clinical and therapeutic side of pH-sensitive liposomes would enable their commercial utility in cancer treatment.

6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.

Objective: The objective of this study was to determine whether the retention of celecoxib in inflamed articular joints of arthritic rats could be enhanced by incorporation of the drug into solid lipid nanoparticles., Methods: Celecoxib-loaded solid lipid nanoparticles (SLN) were prepared by emulsification and high-pressure homogenisation, then characterised by particle size analysis and scanning electron microscopy. In vitro drug-release studies indicated that the nanoparticles exhibited sustained release of celecoxib and the release pattern followed quasi-Fickian diffusion. The biocompatibility of solid lipid nanoparticles was evaluated by histopathology of the rat joints after intra-articular injection in normal rats. Celecoxib and celecoxib-loaded SLN were labelled with (99m)Tc and the labelling parameters were optimised to obtain maximum labelling efficiency. The labelled complexes were administered intra-articularly and the pharmacokinetics and biodistribution were determined., Results: The nanoparticles showed no inflammatory infiltrates 3 and 7 days post-intra-articular injection, proving their biocompatibility and suitability for intra-articular use. Free celecoxib underwent rapid clearance from the inflamed articular joints into the systemic circulation, while the celecoxib-loaded SLN were associated with significantly lower blood levels compared with free celecoxib. Free celecoxib was found to have been extensively distributed to organs of the reticuloendothelial system such as the liver, lungs and spleen. In contrast, celecoxib-loaded nanoparticles demonstrated significantly lower distribution to the reticuloendothelial organs. The articular concentrations of celecoxib-loaded nanoparticles in the inflamed joints were 16-fold higher at 4 hours post-injection and 15-fold higher at 24 hours post-injection than free celecoxib concentrations, indicating greater and prolonged retention in the inflamed articular joints., Conclusion: Celecoxib-loaded SLN with its greater intra-articular retention and sustained-release properties would be a beneficial delivery system for the effective treatment of arthritis and is expected to result in prolonged anti-arthritic activity of celecoxib.

Etoposide-loaded biodegradable microspheres of poly lactic-co-glycolide (PLGA) 50:50, PLGA 75:25, and polycaprolactone (PCL) were prepared by simple o/w emulsification solvent evaparation method and characterized by size analysis and microscopy. The influence of drug to polymer ratio on the entrapment of etoposide was studied. Of all the three types of microspheres, polycaprolactone microspheres (PCL MS) showed the highest entrapment efficiency (94.64%), followed by PLGA 75:25 microspheres (PLGA 75:25 MS) (88.64%) and PLGA 50:50 microspheres (PLGA 50:50 MS) (79.19%). The drug to polymer ratio of 1:20 gave the highest entrapment efficiency for all the three types of microspheres. The in vitro release of etoposide from the three microsphere formulations were studied in phosphate buffer pH 7.4 (pH 7.4 PB) containing 0.1% Tween 80. The microspheres showed an initial burst release, which was highest from the PLGA 50:50 MS and least from the PCL MS. PCL MS microspheres showed the lower and slow drug release than the remaining formulations. The release of etoposide from all the three microsphere formulations followed Higuchi's diffusion pattern. The microspheres in the dissolution medium for 28 days appeared irregular in shape and slightly fragmented.

The main purpose of this work was to develop an oral microemulsion formulation for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was developed for oral delivery of acyclovir. Phase behavior and solubilization capacity of the microemulsion system were characterized, and in vivo oral absorption of acyclovir from the microemulsion was investigated in rats. A single isotropic region, which was considered to be a bicontinuous microemulsion, was found in the pseudoternary phase diagrams developed at various Labrasol:Plurol Oleique:Labrafac ratios. With the increase of Labrasol concentration, the microemulsion region area and the amount of water and Labrafac solubilized into the microemulsion system increased; however, the increase of Plurol Oleique percentage produced opposite effects. The microemulsion system was also investigated in terms of other characteristics, such as interfacial tension, viscosity, pH, refractive index, diffusion, and bioavailability. Acyclovir, a poorly soluble drug, displayed high solubility in a microemulsion formulation using Labrafac (10%), Labrasol (32%), Plurol Oleique (8%), and water (50%). The in vitro intraduodenal diffusion and in vivo study revealed an increase of bioavailability (12.78 times) after oral administration of the microemulsion formulation as compared with the commercially available tablets.

The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34 degrees C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29 degrees C for 18% PF127 to 23.9 degrees C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF127 gel formulation of sumatriptan with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

The Lightcycler Staphylococcus kit is a diagnostic tool for direct real-time detection of Staphylococcus aureus in clinical materials. We show here that detection of S. aureus nasal carriage using this test is hampered by competition of DNA from coagulase-negative staphylococci. However the test is well suited for species identification after culture and the identification of high-load S. aureus carriers.

Microemulsions are clear, transparent, thermodynamically stable dispersions of oil and water, stabilised by an interfacial film of surfactant frequently in combination with a co-surfactant. Recently, there has been a considerable interest for the microemulsion formulation, for the delivery of hydrophilic as well as lipophilic drug as drug carriers because of its improved drug solubilisation capacity, long shelf life, easy of preparation and improvement of bioavailability. In this present review, we discuss about the various advantages of microemulsion in pharmaceuticals, along with its composition variables, physicochemical characterisation etc. The potential use of microemulsion for therapeutic application is also discussed.

Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 500C, compared to those stored at 30 degrees C and 4 degrees C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC-loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t(1/2) and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.

The aim of this study was to evaluate the efficiency of the Pró-Fono Facial Exerciser (Pró-Fono Productos Especializados para Fonoaudiologia Ltda., Barueri/SP, Brazil) to decrease bruxism, as well as the correlation between the masseter and the buccinator muscles using electromyography (EMG). In this study, 39 individuals ranging from 23 to 48 years of age were selected from a dental school and then underwent surface EMG at three different periods of time: 0, 10, and 70 days. They were divided into a normal control group, a bruxer control group (without device), and an experimental bruxer group who used the device. The bruxer group showed a greater masseter EMG amplitude when compared to the normal group, while the experimental group had deceased activity with a reduction in symptoms. The buccinator EMG spectral analysis of the experimental bruxist group showed asynchronous contractions of the masseter muscle (during jaw opening) after using the Pró-Fono Facial Exerciser. The normal group also showed asynchronous contractions. Upon correlation of the data between these muscles, the inference is that there is a reduction in bruxism when activating the buccinator muscle.

The aim of the study was to prepare etoposide-loaded nanoparticles with glyceride lipids and then characterize and evaluate the in vitro steric stability and drug release characteristics and stability. The nanoparticles were prepared by melt emulsification and homogenization followed by spray drying of nanodispersion. Spray drying created powder nanoparticles with excellent redispersibility and a minimal increase in particle size (20-40 nm). Experimental variables, such as homogenization pressure, number of homogenization cycles, and surfactant concentration, showed a profound influence on the particle size and distribution. Spray drying of Poloxamer 407-stabilized nanodispersion lead to the formation of matrix-like structures surrounding the nanoparticles, resulting in particle growth. The in vitro steric stability test revealed that the lipid nanoparticles stabilized by sodium tauroglycocholate exhibit excellent steric stability compared with Poloxamer 407. All 3 glyceride nanoparticle formulations exhibited sustained release characteristics, and the release pattern followed the Higuchi equation. The spray-dried lipid nanoparticles stored in black polypropylene containers exhibited excellent long-term stability at 25 degrees C and room light conditions. Such stable lipid nanoparticles with in vitro steric stability can be a beneficial delivery system for intravenous administration as long circulating carriers for controlled and targeted drug delivery.

Background: In spite of a monocortical design, miniplate osteosynthesis can injure dental roots directly as well as damage dental substance indirectly by interrupting the apical blood stream., Purpose: The present retrospective study classifies different types of dental root trauma caused by monocortical screws, suggests therapeutic options based on diagnosis, and documents survival probability and prognosis after tooth trauma., Patients and Methods: During a period of 11 years, 380 patients with permanent dentition underwent miniplate osteosynthesis for the treatment of mandibular fractures, 29 of whom sustained dental root trauma caused by drilling failure. These patients were clinically and radiographically examined for a follow-up time of not less than 38 months., Results: The 29 patients could be classified into four different types of dental root trauma: 13 pulp injuries above the apical third of the root (type Ia), 6 pulp injuries in the apical third of the root or extradental lesions interrupting the apical blood stream (type Ib), 4 lesions to the central radicular dentin without pulp injury (type II), and 6 lesions to the peripheral radicular dentin and root cementum (type III). Of 13 type Ia injuries, 5 developed apical periodontitis and dilatation of the periodontal space. Therefore one root canal treatment and three apicoectomies were performed. One tooth had to be extracted. Three further type Ia injuries and two type Ib injuries showed root resorptions inducing two root canal treatments. One of six type Ib injuries required root canal treatment because of apical periodontitis. One of four type II injuries caused root resorption not requiring therapy. No relevant, pathological finding could be identified after type III injury., Conclusions: The type of dental root trauma caused by miniplate osteosynthesis determines therapy, complication rate, and survival of the injured tooth.

Purpose: We planned to optimize the effect of formulation variables on the percent drug entrapment (PDE) of the liposomes encapsulating leuprolide acetate by reverse phase evaporation method using Artificial neural network (ANN) and Multiple linear regression (MLR)., Method: Twenty seven formulations were prepared based on 3x3 factorial design. The volume of aqueous phase (X(1)), HSPC/DSPG [negative charge] (X(2)), and HSPC/Cholesterol (X(3)) were selected as the causal factors. Potential variables such as concentration of lipid: drug and hydration medium were kept constant in experimental design. The PDE (dependent variable) and the transformed values of independent variables were subjected to multiple regression analysis to establish a second order polynomial equation (full model). A set of PDE and causal factors was used as tutorial data for the ANN and fed into a computer. The feed forward back propagation (bp) method was optimized. The ANN model and MLR were validated for accurate prediction of PDE., Results: To simplify the polynomial equation, F-statistic was applied to reduce polynomial equation (reduced model) by neglecting non-significant (P<0.05) terms. The reduced polynomial equation was used to plot three two-dimensional contour plots at fixed levels of -1, 0 and 1 of the variable X(3) to obtain various combination values of the two other independent variables (X(1) and X(2)) at predetermined PDE. The root mean square value of the trained ANN model by feed forward bp method was 0.0000354, which indicated that the optimal model was reached. The optimization methods developed by both ANN and MLR were validated by preparing another six liposomal formulations. The predetermined PDE (from ANN and MLR) and the experimental data were compared with predicted data by paired "t" test, no statistically significant difference was observed. ANN showed less error compared to MLR., Conclusions: These findings demonstrate that the ANN model provides more accurate prediction and is quite useful in the optimization of pharmaceutical formulations when compared to multiple regression analysis method. The normalized error (NE) value observed with the optimal ANN model was 0.0211 while it was 0.0658 for the full model in the case of second-order polynomial equation composed of the combination of causal factors (X(1), X(2) and X(3)). Thus the derived equation, contour plots and ANN helps in predicting the values of the independent variables for maximum PDE in the preparation of leuprolide acetate liposomes by reverse phase evaporation technique.

The study evaluates the capability of tripalmitin nanoparticles in enhancing the tumor uptake of etoposide, and the influence of administration route on the biodistribution and tumor uptake of etoposide loaded tripalmitin (ETPL) nanoparticles in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by the spray drying of nanodispersion. Characterization of the nanoparticles was done by particle size analysis, zeta potential measurement and scanning electron microscopy. The size of ETPL nanoparticles was 387 nm and possessed negative charge. Etoposide and ETPL nanoparticles were radiolabeled with 99mTc with high labeling efficiency. The labeled complexes showed good in vitro stability in the presence of DTPA/cysteine and serum stability. Etoposide and ETPL nanoparticles were injected by subcutaneous, intravenous or intraperitoneal routes and their biodistribution and tumor uptake were determined. Subcutaneous injection reduced the distribution of ETPL nanoparticles to all the tissues studied whereas after intraperitoneal injection, the distribution of ETPL nanoparticles to tissues was higher than free etoposide. The intravenous injection resulted in lower concentrations of ETPL nanoparticles in the organs of RES compared to free etoposide. ETPL nanoparticles experienced significantly high brain distribution after intraperitoneal injection indicating its potential use in targeting etoposide to brain tumors. After subcutaneous injection, the tissue distribution of ETPL nanoparticles increased with time indicating their accumulation at the injection site for a longer time. The tumor uptake of both etoposide and ETPL nanoparticles was significantly high after subcutaneous injection (P<0.001) compared to the other routes of administration. The tumor concentration of ETPL nanoparticles after subcutaneous injection was 59 folds higher than that obtained after intravenous and 8 folds higher than after intraperitoneal route at 24 h post-injection. The tumor concentration of ETPL nanoparticles increased with time after subcutaneous injection indicating the slower and progressive penetration from the injection site into the tumor. The study signifies the advantage of incorporating etoposide into tripalmitin nanoparticles in controlling its biodistribution and enhancing the tumor uptake by several folds. The study also reveals that, of the three routes investigated, subcutaneous injection is the route of preference for facilitating high tumor uptake and retention and is likely to have greater antitumor effect resulting in tumor regression.

Cancer chemotherapeutic agents are often administered systemically. Following systemic administration, numerous biological factors associated with the tumours influence the delivery of the drugs to the tumours. These factors have been extensively studied for the last 2 decades. The influence of these biological factors has brought about a drastic change in the design of drug delivery systems to solid tumours. This review discusses the various biological factors influencing drug delivery to tumours and the subsequent development of injectable delivery systems (i.e., lipid-based nanoparticles (SLNs)) for adequate delivery of drug to solid tumours.

Background: Up to now the results after condylar reconstruction of the mandible have been regarded as less than satisfactory., Purpose: Functional and aesthetic long-term results after condylar head resection in traumatic and tumour cases with or without replacement by a metallic condylar head prosthesis were compared in a retrospective study., Patients and Methods: From 1980 to 2001, 23 temporomandibular joints of 19 patients were reconstructed with metallic condylar head prostheses. The resected region, the contralateral joint, facial and masticatory muscles and the dental system were clinically and radiographically monitored for a mean period of 4 years and 9 months. Seven patients who underwent condylar resection without substitution were observed over an average follow-up time of 7 years and 11 months., Results: Patients who underwent condylar resection without substitution reported more trouble with eating and speaking for a long time. TMJ endoprostheses preserved facial symmetry better. Maximum mandibular opening as well as lateral and protrusive excursions were slightly reduced in comparison with both unaffected controls and patients who underwent condylar resection without substitution. In this study bilateral condylar prostheses exhibited the same functional and aesthetic results as unilateral arthroplasty., Conclusions: Metallic condylar head prostheses originally developed for temporary replacement worked in some cases as long-term joint replacement but were not able to reach the total functional quality of natural temporomandibular joints.

A non-bitter chloroquine suspension formulation for pediatric use was prepared in the form of an ion-pair of chloroquine with pamoic acid. Various parameters involved in the formulation of a stable and palatable suspension have been optimized. The suspension was characterized for particle size analysis, viscosity, physical and chemical stability and taste. Release of chloroquine from the ion-pair conducted as dissolution rate studies in simulated gastric media showed near to 100% release instantaneously. In-vivo bioavailability study conducted in albino rats indicated comparable bioavailability of chloroquine from the suspension with that of chloroquine phosphate syrup taken as standard. Stability study conducted over a period of 3 months showed the intactness of the ion-pair and the tasteless behavior of the suspension throughout the period of storage.

The aim of the study is to determine and compare the pharmacokinetics and tissue distribution of Doxorubicin (Dox) delivered as solution or through nanoparticles after intravenous (i.v.) and intraperitoneal (i.p.) injection. Doxorubicin loaded poly(butyl cyanoacrylate) nanoparticles were synthesized by dispersion polymerization (DP) and emulsion polymerization (EP) techniques. The drug loaded DP and EP nanoparticles were administered by i.v. or i.p. routes and the respective pharmacokinetics and tissue distribution were determined. Both types of nanoparticles significantly enhanced the elimination half-life (T(1/2)), mean residence time (MRT) AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox in blood after i.v. injection. Dox delivered through DP nanoparticles rapidly disappeared from blood and distributed to the organs of reticuloendothelial system (RES). But, the clearance of Dox delivered through EP nanoparticles from blood was slower than this of the DP nanoparticles and Dox solution. After i.p. injection, the Dox loaded into DP nanoparticles quickly appeared in blood and undergone rapid distribution to the organs of RES, while the Dox loaded into EP nanoparticles absorbed slowly into blood and remained in the circulation for longer time. The absorption into blood of Dox delivered through DP and EP nanoparticles after i.p. injection was relatively rapid and higher than Dox solution. The T(1/2), MRT, AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox in blood were significantly higher and the clearance (Cl) was lower than for the Dox solution after i.p. injection. The tissue concentrations of Dox delivered through nanoparticles after i.p. injection were significantly lower than after i.v. injection. The bioavailability (F) of Dox was greatly enhanced by DP (approximately 1.9 fold) and EP nanoparticles (approximately 2.12 fold) compared to Dox solution after i.p. injection. EP nanoparticles significantly enhanced the bioavailability, MRT, T(1/2), AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox than DP nanoparticles. This signifies the advantage of EP nanoparticles in increasing the elimination half-life of Dox both after i.v. and i.p. injection and enhanced bioavailability after i.p. injection, which is expected to improve the therapeutic efficacy of Dox and reduce the Dox-associated systemic toxicity. Importantly, both DP and EP nanoparticles greatly reduced the distribution of Dox to heart both after i.v. and i.p. injection, suggesting their potential in reducing Dox-associated cardiotoxicity.

This study deals with the study of the optimization of the volume of organic phase (X1), the volume of aqueous phase (X2), and the drug:phosphotidylcholine (PC): cholesterol (Chol) molar ratio (X3) using 3(3) factorial 26-term logit model to maximize the Flutamide absorption at the target site in the treatment of prostatic cancer by maximizing the entrapment of Flutamide (FLT) in the preparation of FLT liposomes. FLT liposomes are expected to be an excellent carrier for FLT to the prostatic cancer site based on the use of liposomes with other drugs. A 3(3) factorial 26-term logit model for coded factors X1, X2, and X3 is used to develop a second-order response surface regression equation for predicting percent entrapment efficiency (%EE) for FLT. In turn, the regression equation is used to develop contour plots that show the %EE is maximized at the level of 1:15:2 of the drug: PC: Chol molar ratio with the volume of organic phase (chloroform: methanol) (1:2) at 5 mL and the volume of distilled water at 1.5 mL.

The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with( 99m)Tc and injecting intraarticularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres.

The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.

We sought to evaluate our experience concerning the high waiting list mortality rate for orthotopic liver transplantation (OLT) using the MELD (Model for End-Stage Liver Disease), which has been shown to predict short-term survival better than Child-Turcotte-Pugh (CTP) classification. The predominant end-stage disease was cirrhosis due to hepatitis C virus (67%), patient mean age was 36.8 years, and 72.1% were men. When the patients were included on a waiting list, the MELD score was stratified into W: 0 to 10; X: 11 to 20, and Y: 21 to 40 and the CPT as A: 5 to 6, B: 7 to 9, and C: 10 to 15. It was also observed that 77.8% of patients were on the waiting list, 16.4% underwent OLT and 5.8% had been removed. The estimated survival rate after 1 year was W = 85.4%; X = 83.3%, Y = 46.8%; A = 81.3%, B = 84.2%, C = 45.9%. Child median score was 8 +/- 1.5 (5 to 15) and the MELD was 14.7 +/- 5.1 (8 to 43). The mortality rate was 20.2%. Severe patients classified as Y or C showed greater mortality than the other groups (P <.001), but no significant difference between Y and C strata. The mortality rate was the same as in previous years.

The purpose of this study was to prepare conventional and sterically stabilized liposomes containing leuprolide acetate in an attempt to prolong the biological half life of the drug, to reduce the uptake by reticuloendothelial system (RES), and to reduce the injection frequency of intravenously administered peptide drugs. The conventional and sterically stabilized liposomes containing leuprolide acetate were prepared by reverse phase evaporation method and characterized for entrapment efficiency and particle size. Radiolabeling of leuprolide acetate and its liposomes was performed by direct labeling with reduced technetium-99m. Its biodistribution and imaging characteristics were studied in ehrlich ascites tumor (EAT)-bearing mice after labeling with technetium-99m. The systemic pharmacokinetic studies were performed in rabbits. A high uptake by tumor was observed by sterically stabilized liposome containing leuprolide acetate compared with free drug and conventional liposomes. The liver/tumor uptake ratio of free drug, conventional (LL), and sterically stabilized liposomes (SLL5000 and SLL2000) was found to be 20, 7.99, 1.63, and 1.23, respectively, which showed the increased accumulation of sterically stabilized liposomes in tumor compared with the free drug and conventional liposomes at 24 hours postinjection. Liver uptake of sterically stabilized liposomes was still 7-fold less than the conventional liposomes. The marked accumulation of liposomes in the tumor-bearing mice was also documented by gamma scintigraphic studies. The findings demonstrate the distribution of these liposomes within solid tumor and prove that the sterically stabilized liposomes experience increased tumor uptake and prolonged circulation half life. Hence these findings will be relevant for the optimal design of long circulating liposomes for the peptide drugs and for targeting of liposomes toward tumor.

The objective of this study is to enhance the delivery of Doxorubicin hydrochloride to Dalton's lymphoma solid tumour through poly(butyl cyanoacrylate) (PBC) nanoparticles. Doxorubicin loaded PBC (DPBC) nanoparticles were prepared by emulsion polymerization and characterized by particle size analysis, zeta potential and scanning electron microscopy. Doxorubicin HCl (Dox) and DPBC nanoparticles were radiolabeled with 99mTc by reduction method using stannous chloride and optimized the labeling parameters to obtain high labeling efficiency. The in vitro stability of 99mTc-labeled complexes was determined by DTPA and cysteine challenge test. The labeled complexes showed very low transchelation and high in vitro and serum stability. 99mTc labeled complexes of Dox and DPBC nanoparticles were administered subcutaneously below the Dalton's lymphoma tumour and biodistribution was studied. The distribution of DPBC nanoparticles to the blood, heart and organs of RES such as liver, lung and spleen was biphasic with a rapid initial distribution, followed by a significant decrease later at 6 h post-injection. The distribution of Dox to tissues was very low initially and increased significantly at 6 h post-injection indicating its accumulation at the injection site for a longer time. The concentration of DPBC nanoparticles was also found high in tissues at 6 h post-injection indicating their accumulation at the subcutaneous site and consequent disposition to tissues with time. A significantly high tumour uptake of DPBC nanoparticles (approximately 13 fold higher at 48 h post-injection) (P <0.001) was found compared to free Dox. The tumour concentrations of both Dox and DPBC nanoparticles increased with time indicating their slow penetration from the injection site into tumour. The concentration of DPBC nanoparticles in the femur bone in the tumour region was also significantly higher (P <0.001) than free Dox and increased with time. The study signifies the advantage of delivering Dox to Dalton's lymphoma through PBC nanoparticles by facilitating enhanced tumour uptake and prolonged tumour retention, which are expected to lead to greater therapeutic effect in the form of tumour regression.

We investigated the effect of UV-B irradiation on PI 3-kinase activity in human fetal hepatocytes. When cells were exposed to monochromatic (304nm) UV-B light, a significant increase in intracellular PI 3-kinase activity was observed in a dose dependent manner with maximal activity upon 1500 Jm(-2) irradiation. At 1500 Jm(-2) dose PI 3-kinse activity increased by 80% in membrane fraction of fetal hepatocytes of 25 weeks gestation. PI 3-kinse inhibitors wortmannin and LY294002 specifically inhibited the UV-B induced lipid kinase activity and blocked significantly the UV-B induced cell viability. The data suggests a correlation between cell survival and elevated levels of PI 3-kinase and suggest that UV-B irradiation at a dose of 1500 Jm(-2) is ideal for fetal hepatocyte transplantation. Also, PI 3-kinase levels could be a representative marker for viable UV-B irradiated fetal hepatocytes for transplantation.

Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, (99m)Technetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P < 0.005) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.

Background: Adenomatoid odontogenic tumors (AOT) and calcifying odontogenic cysts (COC, Gorlin's cyst) are rare benign specificities of odontogenic tumors. Most odontogenic tumors are lesions of embryonic odontogenic tissue. Radiographically, odontogenic tumors may mimic an odontogenic follicular cyst., Case Report: This paper describes the case of an 11-year-old female patient with a remarkable combination of these two entities. The lesions were found at the site of a retained first premolar and a persistent deciduous tooth 84 of the right lower jaw. Without clinical symptoms the tumor had expanded the vestibular cortical bone of the premolar region. Radiographically, the lesion appeared as a typical follicular cyst. During the operation, excochleation of the cyst was performed and the premolar was extracted. Finally, the epithelium of the cyst was treated by curettage. The histologic specimen revealed the diagnosis of an adenomatoid odontogenic tumor (AOT) in a calcifying odontogenic cyst (COC)., Discussion: The described case shows that symptoms of odontogenic tumors are usually nonspecific. For that reason one should always take a biopsy for histological investigation when patients present atypical cysts of the jaw. In rare cases even malignant odontogenic neoplasms could occur.

Dentogenous inflammatory diseases can lead to typical dermatological facial symptoms with formation of cutaneous sinuses. Partsch's chronic granulomatous inflammation can result from conducted inflammation of a nonvital tooth via a chronic apical inflammation. In this rare disease, the granulomatous tissue perforates the bone, channels through the overlying skin, and drains via cutaneous or oral sinuses. A frequent localization of the cutaneous sinus is the skin inferior to the body of the mandible, and it is caused by an inflammation of the lower molars. Treatment consists of identifying the responsible teeth and eliminating the focus of infection. Chronically progressive periradicular granuloma and/or radicular cysts can be present with impressive dermatological symptoms. Therefore, X-ray examinations are necessary to exclude possible dentogenic causes in cases of badly healing processes of the face or neck.

Case: Unilateral necrosis of the tongue is an uncommon symptom of different rare diseases. Previously, it had only been described as an infrequent complication of temporal arteritis or as a side effect of therapy with ergotamine. We present a case of unilateral necrosis of the tongue in a 62-year-old woman with invasive ductal carcinoma of the breast treated with epirubicin and cyclophosphamide., Results: The necrosis led to a rapid swelling of the tongue and consequently to an airway obstruction necessitating a tracheotomy. After excision of the necrosis, the swelling of the tongue and the airway obstruction subsided., Discussion: Because of the temporal connection between the occurrence of the necrosis and the administration of chemotherapy, an adverse effect of the administered drugs seems most likely. However, a paraneoplastic pathogenesis cannot be completely excluded. The occurrence of unilateral necrosis of the tongue is a rare complication of the above-mentioned conditions. However, it is important to be aware of the different causes leading to this rare disease in order to initiate the right therapy.

The present study investigated the effect of charge (neutral, negative and positive) on liposomal membrane on the distribution of cyclosporine encapsulated in it to various organs. Liposomes were prepared by using different phospholipids by thin film hydration followed by sequential extrusion through polycarbonate membranes to achieve a desired particle size, with high entrapment efficiency and then lyophilised using sucrose as cryoprotectant. The possible in vivo distribution of cyclosporine and its liposomes after direct labeling with reduced technetium-99m has been studied in mice. The blood kinetics and biodistribution study of these labeled complexes shows prolonged circulation of positive and neutral charged liposomes in blood compared to free drug and negative charged liposomal formulation. The biodistribution of the tagged liposomes confirms that increased radioactivity was seen in liver and spleen, with minimal involvement of the kidney. At 4 h post injection the biodistribution data in kidney reveals approximately 1-2% of the injected dose was present for cyclosporine loaded liposomes, which elicits the possibility of reducing the nephrotoxicity, generally seen in free cyclosporine. Interestingly, the biodistribution and gamma imaging studies of the charged cyclosporine liposomes indicated that an appreciable amount of these labeled complexes goes to bone marrow when compared to the free cyclosporine. The findings demonstrate the distribution of these liposomes within various organs and proved that the positively charged liposomes experience increased bone uptake and prolonged circulation half-life. Hence this finding implies the possibility of using these formulations for liver and bone marrow transplantation.