Development of a quality assessment tool for pharmacy and therapeutics committees and subsequent pilot testing.

Pharmacy and therapeutics committees (PTCs) are multidisciplinary hospital teams responsible for rational medication use. We aimed at developing and piloting an assessment tool for their operating quality.We conducted a scoping literature review in PubMed and Embase to identify potential assessment items. Their relevance was systematically rated and consolidated into the final tool.60 relevant items were included, grouped into eight focus topics: the committee's institutional integration, member characteristics, performance indicators, meeting structure, formulary decision-making and characteristics, strategies to guide medication use and medication use evaluations.In combination with a SWOT (strengths, weaknesses, opportunities and threats) analysis, the tool helped the identification of improvement opportunities for a pilot hospital: adapting the committee's structure, improving the formulary decision-making, implementing strategies to guide formulary medication use and strengthening the committee's recognition within the institution.The tool successfully identified improvement opportunities for a PTC and could therefore be interesting for other hospitals.

Absceso periamigdalino bilateral en pediatría: reporte de un caso / Bilateral peritonsillar abscess in children: case report

El absceso periamigdalino es la complicación más frecuente de la amigdalitis aguda bacteriana, definido como la presencia de pus entre la cápsula periamigdalina y el músculo constrictor superior de la faringe. Habitualmente, su presentación es unilateral; es rara su afectación bilateral. Es más frecuente en adultos y poco común en niños. Cuando es bilateral, el paciente presenta odinofagia, trismus, sialorrea, fiebre y voz gutural, síntomas que comparte con el absceso unilateral, pero, en el examen físico, se evidencia abombamiento de ambos pilares anteriores, edema de úvula y paladar blando, sin asimetrías de las estructuras faríngeas. Se requiere un alto nivel de sospecha clínica para lograr el diagnóstico temprano. El manejo de la vía aérea, que podría ser dificultoso, es un aspecto importante en el tratamiento. Se presenta el caso clínico de un niño con absceso periamigdalino bilateral; se describe el proceso diagnóstico y terapéutico.

Peritonsillar abscess is the most common complication of acute bacterial tonsillitis, defined as the presence of purulent exudate between the peritonsillar capsule and the superior constrictor muscle of the pharynx. Usually, its presentation is unilateral; its bilateral involvement is rare. It is more common in adults, being uncommon in children. Clinically, it presents odynophagia, trismus, sialorrhea, fever, guttural voice, symptoms that it shares with the unilateral abscess, evidencing in the physical examination bulging of both anterior pillars, edema of the uvula and soft palate, but without asymmetries of pharyngeal structures. A high level of clinical suspicion is required to achieve early diagnosis. The management of the airway, which could be difficult, is an important aspect in the treatment. It is reported the clinical case of a child with bilateral peritonsillar abscess, the diagnostic and therapeutic process.

[Bilateral peritonsillar abscess in children: case report]. / Absceso periamigdalino bilateral en pediatría: reporte de un caso.

Peritonsillar abscess is the most common complication of acute bacterial tonsillitis, defined as the presence of purulent exudate between the peritonsillar capsule and the superior constrictor muscle of the pharynx. Usually, its presentation is unilateral; its bilateral involvement is rare. It is more common in adults, being uncommon in children. Clinically, it presents odynophagia, trismus, sialorrhea, fever, guttural voice, symptoms that it shares with the unilateral abscess, evidencing in the physical examination bulging of both anterior pillars, edema of the uvula and soft palate, but without asymmetries of pharyngeal structures. A high level of clinical suspicion is required to achieve early diagnosis. The management of the airway, which could be difficult, is an important aspect in the treatment. It is reported the clinical case of a child with bilateral peritonsillar abscess, the diagnostic and therapeutic process.

El absceso periamigdalino es la complicación más frecuente de la amigdalitis aguda bacteriana, definido como la presencia de pus entre la cápsula periamigdalina y el músculo constrictor superior de la faringe. Habitualmente, su presentación es unilateral; es rara su afectación bilateral. Es más frecuente en adultos y poco común en niños. Cuando es bilateral, el paciente presenta odinofagia, trismus, sialorrea, fiebre y voz gutural, síntomas que comparte con el absceso unilateral, pero, en el examen físico, se evidencia abombamiento de ambos pilares anteriores, edema de úvula y paladar blando, sin asimetrías de las estructuras faríngeas. Se requiere un alto nivel de sospecha clínica para lograr el diagnóstico temprano. El manejo de la vía aérea, que podría ser dificultoso, es un aspecto importante en el tratamiento. Se presenta el caso clínico de un niño con absceso periamigdalino bilateral; se describe el proceso diagnóstico y terapéutico.

Cloning of the pig PEPT2 (pPEPT2) and characterization of the effects of epidermal growth factor (EGF) on pPEPT2-mediated peptide uptake in the renal porcine cell line LLC-PK1.

The renal di/tri-peptide transporter PEPT2 is situated in the distal parts of the proximal tubule, where it mediates reabsorption of peptides from the primary urine. The transporter has been thoroughly characterised with respect to substrate-affinity relationships, however little is known about its regulation. Previous studies from our group have shown that epidermal growth factor (EGF) down-regulates PepT2 in the rat proximal kidney tubule cell line SKPT0193 cl.2. The aim of the present work was to clone the pig PEPT2 (pPEPT2) and to study the effect of EGF on pPEPT2 expression in the porcine kidney cell line LLC-PK1. pPEPT2 from LLC-PK1 cells was PCR-cloned. The predicted protein consisted of 729 amino acids, had a molecular mass of 81.7 kDa and was 88% identical and 94% similar to hPEPT2, thus displaying a close similarity to the human orthologue. pPepT2 expressing LLC-PK1 cells were cultured in the absence and presence of EGF in the culture media. EGF induced an increase in uptake of (14)C-glycylsarcosine ([(14)C]-Gly-Sar), accompanied by an increase in transcellular electrical resistance, total cell protein, alkaline phosphatase activity and cell density. The increase in uptake of [(14)C]-Gly-Sar was maximal when cells were cultured in the presence of EGF throughout the culture period of 10 days. The EGF-treatment did not induce significant changes in pPepT2 mRNA expression, as determined by real-time PCR. The effect of EGF thus appears to be an increase in the number of cells without a loss of differentiation, an effect which is quite different from earlier observations on the SKPT cell line.

Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media.

The rat proximal kidney tubule cell line SKPT-0193 cl.2 (SKPT) expresses the di-/tripeptide transporter PEPT2 (rPEPT2) and has been used to study PEPT2-mediated transport. Traditionally, SKPT cells have been cultured in growth media supplemented with epidermal growth factor (EGF), apotransferrin, dexamethasone, and insulin. It was recently demonstrated that omission of EGF from the culture media caused a drastic increase in the expression of rPEPT2. The hypothesis was therefore that the SKPT cell line might be able to differentiate and express rPEPT2 in the absence of the four agonists traditionally added. The aim of the study was thus to characterize Gly-Sar transport parameters in SKPT cells cultured in basic growth media (conventional media without added agonists). Morphology was studied using confocal laser scanning microscopy (CLSM) and immunohistochemistry. Monolayer integrity was evaluated using transepithelial electrical resistance (TEER) measurements and [(3)H]-mannitol permeabilities. Di-/tripeptide transporter activity was studied using [(14)C]-glycylsarcosine ([(14)C]-Gly-Sar). SKPT cells grown in basic media for 4 days formed confluent monolayers with a TEER of 5.03 +/- 0.33 kOmega.cm(2) (n = 5). Apical Gly-Sar uptake peaked after 3-6 days in culture. Uptake at day 4 was 5.89 +/- 0.30 pmol.cm(-2).min(-1) (n = 3). Di-/tripeptide uptake displayed an optimum at approximately pH 6. Affinity values for cephalexin, kyotorphin, and delta-aminolevulinic acid were comparable to those obtained in other PEPT2-expressing model systems. It can be concluded that SKPT cells grown in the absence of the agonists traditionally added to the culture media retain all necessary properties for PEPT2-mediated peptide uptake studies. Furthermore, the absence of the agonists might facilitate studies of hormonal regulation of PEPT2 expression and transport activity.

Nonviral gene delivery systems: From simple transfection agents to artificial viruses.

The introduction of nucleic acids into cells for therapeutic intervention is greatly impeded by the size and charge of these molecules and therefore requires sophisticated vectors that facilitate cellular uptake. Both viral and nonviral vectors have been developed for this purpose, each with their own advantages and shortcomings. The engineering of artificial viruses by dismantling virus particles or incorporating viral features into nonviral vectors represents a novel strategy to combine "the best of both worlds".:

Swellable matrices for the controlled-release of diclofenac sodium: formulation and in vitro studies.

Oral administration has been the most usual and convenient employed route of drug delivery systems. Particularly, oral sustained-release systems for the delivery of drugs by a process of continuous swelling of the polymeric carrier have been investigated. Thus, the goal of this study was to evaluate the effects of hydroxypropyl methylcellulose (HPMC) and carboxypolymer (Carbopol 934) on the release behavior of diclofenac sodium (DS) from a swellable matrix tablet system. Nine different DS controlled-released tablets were compressed by using the wet-granulation technology. The influence of the polymer content, the polymer ratio, the polymeric swelling behavior, and the pH changes on the release rate of DS was investigated. There was no significant difference in drug release when total polymer concentration was 10%. When the tablets were formulated having 20% or 30% of HPMC/carbomer, it was observed that a more rapid release of DS occurred as the carboxypolymer ratio within the matrices increased. In agreement with previous results, the dissolution studies demonstrated that the combination of these two polymeric matrix formers resulted in near zero-order release rate of DS. The DS release from all these matrix tablets was pH dependent, being markedly reduced at lower pH, and could be attributed to the poor solubility of DS at this pH value. In HCl 0.1 N solution, HPMC controlled drug release because the carbomer has a low solubility at this pH. As the pH increased, the carbomer became ionized, being able to interact with HPMC to control the drug release.

In-depth evaluation of Gly-Sar transport parameters as a function of culture time in the Caco-2 cell model.

The aim of the present study was to investigate the influence of culture time on hPEPT1-mediated transport in Caco-2 cell monolayers. Peptide transport activity in Caco-2 cells grown in standard media and in a "rapid" 4-day model was first compared. The rapid 4-day Caco-2 cell model, cultured using a cocktail of growth factors and agonists, displayed lower peptide uptake capacity than Caco-2 cells grown for 4 days in conventional media, and was judged to be unsuitable for peptide transport studies. Peptide transport activity as well as monolayer integrity and tissue morphology were evaluated in the standard >21 days model as a function of the culture time. Peptide transport activity was studied using [14C]-glycylsarcosine ([14C]-Gly-Sar). Monolayer integrity was evaluated by transepithelial electrical resistance (TEER) measurements and [3H]-mannitol permeabilities. Tissue morphology and hPEPT1 expression were studied using confocal laser scanning microscopy (CLSM) and conventional staining/immunostaining. Caco-2 cells grown in conventional media became confluent after 3-4 days. Mannitol permeability decreased from day 5 to 21 and TEER increased steadily until approximately day 21. Apical hPEPT1 uptake activity appeared to be maximal in cells cultured for >21 days, whereas basolateral uptake reached a maximum already after 12 days in culture. In some of the passages studied, a secondary increase in hPEPT1 transport activity was observed in cells grown for >25 days. A large carrier-mediated transepithelial peptide flux component was evident from day 14.

Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2.

The renal peptide transporter PEPT2 plays an important role in absorption of di- and tripetides in the proximal tubule; however, knowledge of regulation of PEPT2 by growth factors and hormones is limited. In the present study, we examined the effects of epidermal growth factor (EGF) on PEPT2 transport capacity and expression in the rat proximal tubule cell line SKPT0193 cl.2 (SKPT), which expresses rat PEPT2 (rPEPT2) in the apical membrane. Treatment of SKPT cells with EGF during cell culture growth caused a dose-dependent decrease in rPEPT2 transport capacity and expression, as determined by studies of apical uptake of [14C]glycylsarcosine, rPepT2 mRNA levels, and immunostaining of SKPT cells with a rPEPT2-specific antibody. On the contrary, apical uptake of glucose and lysine was increased in EGF-treated cells, indicating that EGF was not acting generally to decrease apical nutrient uptake mechanisms in the proximal tubule cells. Our findings indicate that EGF decreases rPEPT2 expression by lowering transcription of the rat PepT2 gene or by decreasing rat PepT2 mRNA stability. Previous investigators routinely used SKPT cell culture media with a high (10 ng/ml) EGF concentration. Our study suggests that this might be disadvantageous when studying PEPT2-mediated transport phenomena. These findings demonstrate for the first time EGF-mediated regulation of PEPT2 expression in a kidney cell line. The relevance for kidney regulation of peptide transport activity in physiological and/or pathophysiological situations, where EGF and EGF receptor levels change drastically, remains to be established.

In-vitro studies of diclofenac sodium controlled-release from biopolymeric hydrophilic matrices.

PURPOSE: The objective of this study was to develop uncoated HPMC matrix tablets, evaluating the relationship and influence of different content levels of microcrystalline cellulose (MCC), starch, and lactose, in order to achieve a zero-order release of Diclofenac Sodium. METHODS: HPMC matrix tablets of Diclofenac Sodium using microcrystalline cellulose (MCC), starch, and lactose were prepared by wet granulation process. The USP paddle method was selected to perform the dissolution profiles carried out in 900 mL 0.1 N HCl, and phosphate buffer. RESULTS: There was no significant difference in drug release between the hydrophilic matrices when the HPMC concentration was modified in low percentage. Release kinetics of Diclofenac Sodium from these swollen matrices was principally regulated by starch (17 percent) or lactose (17 percent), even on the presence of MCC. When starch (8.5 percent) and lactose (8.5 percent) were mixed at lower concentration in a ratio 1:1, MCC (5 percent or 7,5 percent) appeared to control the drug release. The release profile remained unchanged after three months storage of tablets. The best-fit release kinetics was achieved with the zero-order plot, followed by the Higuchi and first-order equations. The data obtained proved that the formulations are useful for a sustained release of Diclofenac, due to the percentage released after 8 hours is nearly to 70 percent. CONCLUSIONS: The release of Diclofenac Sodium was influenced by the presence of MCC, and by the different concentrations of starch and lactose. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Compared to conventional tablets, release of the model drug from these HPMC matrix tablets was prolonged; as a result, an oral release dosage form to avoid the gastrointestinal adverse effects was achieved.