Bacteria associated with apical periodontitis promotes in vitro the differentiation of macrophages to osteoclasts.

OBJECTIVE: To analyze the possible in vitro effect of the cytokine RANKL and bacteria involved in apical periodontitis on the differentiation of macrophages into osteoclasts. MATERIAL AND METHODS: Bacteria were isolated (mainly E. faecium and E. faecalis) from the root canal of fifty patients with apical periodontitis, the possible effect of these bacteria on the phagocytic activity of the monocyte cell line THP-1 was analyzed by flow cytometry. Furthermore, the effect of these bacteria (alone or in combination with the cytokine RANKL) on the differentiation of THP-1 macrophages into osteoclasts was analyzed through the expression of the receptor RANK and the tartrate-resistant acid phosphatase TRAP. Finally, the release of different cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) by THP-1 cells induced to differentiate into osteoclasts was also analyzed. RESULTS: We observed a significant proportion of THP-1 cells were able to internalize E. faecium and E. faecalis. Furthermore, these bacteria were able to induce (alone or in combination with RANKL) a significant expression of RANK by THP-1 macrophages; accordingly, E. faecium and E. faecalis induced very significant levels of TRAP in these cells. Finally, during the differentiation of THP-1 macrophages induced by RANKL or bacteria, a significant release of the pro-inflammatory cytokines IL-6 and TNF-α was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the causative agents of apical periodontitis can induce the differentiation of osteoclasts as well as the release of pro-inflammatory cytokines, phenomena that may have an important role in the bone damage observed in this condition.

[Phylephebitis due to diverticulitis]. / Pileflebitis secundaria a diverticulitis.

A case of a 52 year-old-male, with past medical history of renoureteral crisis and recurrent episodes of abdominal pain, is presented. The patient presented to the Emergency Department with abdominal pain (similar to previous episodes), fever and abnormal liver function test (marked elevation of gammaglutamyltranspeptidase and alkaline phosphatase). An abdominal ultrasound was performed showing hepatomegaly, and enlarged spleen and an echogenic material that suggested a thrombosis. A CT scan confirmed the thrombosis of the inferior mesenteric vein extending up to the splenic vein and the portal vein. It also showed a large number of diverticulum. Surgery was performed in order to rule out an acute diverticulitis. A phylephlebitis, infective suppurative thrombosis of the portal vein and its branches (inferior mesenteric vein and splenic vein) was found due to an acute diverticulitis with neither perforation nor abscess. A ligature of the inferior mesenteric vein and a Hartmann procedure with resection of the diseased colon, and end colostomy and creation of a rectal stump, were performed. A favourable outcome was obtained with antibiotics and anticoagulation. Some aspects of the aetiology, symptoms, diagnosis and treatment of this unusual complication of diverticulitis are also presented.

Fronts movement as a useful tool for hydrophilic matrix release mechanism elucidation.

The purpose of this study was to modify the fronts movement method proposed by Colombo et al. in order to apply it to uncoloured drugs and hydrophilic non-swellable matrices. Matrix tablets were prepared using theophylline as a model drug and sodium carboxymethylcellulose (NaCMC) or a new graft copolymer, hydroxypropylcellulose methylmethacrylate dried by lyophilization (HCMMAL), as polymer carriers. Drug release experiments were performed from the whole tablets. Radial drug release and fronts movement were also evaluated using special devices consisting of two Plexiglass(R) discs joined by means of four stainless steel screws. Release kinetics were determined by means of Higuchi, Korsmeyer and Peppas equations and were related to the fronts movement data. The analysis of drug release and fronts movement kinetics revealed a different release mechanism for both matrices. Drug release from NaCMC matrices was mostly controlled by relaxation, whereas drug diffusion through the porous network regulated drug release from HCMMAL matrices. A reduction in the surface exposed to the dissolution medium led to a decrease in the drug release rate, but the release mechanism was not essentially modified. Fronts movement was shown as a useful tool for matrix release mechanism elucidation. A new denomination for the different fronts observed in HCMMAL matrices was proposed.

Effect of compression speed and pressure on the physical characteristics of maltodextrin tablets.

The present paper studies the effect of applied pressure (0-300 MPa) and compression speed (8 and 40 cycles/min) on the physical characteristics of four varieties of maltodextrins for direct compression. The materials were tableted by using a single-punch tablet machine. On the basis of the mechanical properties it seems to be reasonable to propose a limit in the plastic deformation and consequently bonding between particles. This limit could be approximately 90 MPa, and it was almost independent of the variety compressed. Disintegration behavior and, most probably, release properties are related with this limit; i.e., mechanical parameters and disintegration time increased as applied pressure was increased up to this limit. Above this limit, no differences of note were found. The different movement of particle layers in the single-sided eccentric profile led to the computation of differences between upper and lower tablet hardness surfaces, which were indicative of a consolidation mechanism. The differences obtained were indicative of the plastic deforming nature of maltodextrins.

Effect of Explotab on the tabletability of a poorly soluble drug.

The efficiency of a superdisintegrant (Explotab) in a direct-compression formulation containing a poorly water soluble drug (albumin tanate) at high dosage was investigated. An experimental design with two variables, applied pressure and concentration of Explotab, enabled its effects on the tableting and the mechanical properties of the final tablets to be determined. Differential scanning calorimetry was performed to study the interactions between drug and excipients. No incompatibility was found between drug-excipient mixtures prepared in the proportion 1:1 and in the corresponding formulation at room temperature and after 3 weeks at 50 degrees C. The concentration of Explotab has a positive effect on flow properties. Also, the effect of applied pressure and disintegrant content was found to be significant on all compressional parameters. At low applied pressures, the breaking strength was independent on Explotab concentration. However, at higher applied pressures, the maximum densification obtained with 10% Explotab produced a limited breaking strength lower than that at 0% concentration. The response surface shows a certain level of Explotab, around 7%, at which the disintegration time was the shortest. At this level, the surface response was independent of the applied pressure. In our study, the experimental design was a valuable tool used to establish the optimum manufacturing conditions.

Frictional work in double-sided tablet compression.

The aim of this study was to evaluate the friction during double-sided tablet compression. Dicalcium phosphate dihydrate and lactose were tabletted with a compaction simulator with symmetrical and asymmetrical double-sided sawtooth punch displacement profiles. The estimation of force transmission in a powder column was based on an exponential equation, including the material parameter consisting of both the friction coefficient and Poisson's ratio. This parameter was predetermined from a single-sided compression. A novel equation was derived from a previously presented equation for friction work in single-sided tablet compression. The basic assumption was drawn from the linearly decreasing movement of infinitely thin particle layers, which are produced as the compressing punch surface approaches the other punch. This calculation was also based on the assumption that the equilibrium point, where the particles do not move, is halfway between the punches in the symmetrical profile and at a distance proportional to the amplitudes of the asymmetrical upper and lower sawtooth profiles. The tensile strength of tablets compressed with single-double-sided profiles was identical, and thus the behavior of the materials studied under compression was independent of the compression profiles. The friction work values that were calculated with the proposed expression for double-sided profiles were close to the theoretical values, as estimated by calculations based on compressions with single-sided profiles. In conclusion, the novel mathematical expression opens new possibilities for the evaluation of friction in double-sided compression; for example, in rotary press tabletting.

Time-dependent densification behaviour of cyclodextrins.

Understanding of volume reduction mechanisms is a valuable aid in the development of robust cyclodextrin tablet formulations. The particle and powder properties of alpha-, beta-, gamma- and hydroxypropyl (HP)-beta-cyclodextrins and their behaviour under compression were examined. The cyclodextrins studied showed big differences in particle-size distribution and particle shape. The highest densification on tapping was found for cyclodextrins having the smallest particle size. Cyclodextrins were compressed using single-sided saw-tooth displacement-time profiles at rates of 3 and 300 mm s-1 with a compaction simulator. The densification of the powders was examined by Heckel treatment, using the tablet-in-die and ejected-tablet methods. The cyclodextrins were denser at the beginning of the tableting process (at low pressures) if high rather than low velocity was used. Ranking according to their tendency toward total deformation and permanent plastic deformation was: HP-beta-cyclodextrin > beta-cyclodextrin > gamma-cyclodextrin > alpha-cyclodextrin. The ranking order in strain-rate sensitivity (SRS) of total deformation was HP-beta-cyclodextrin > > gamma-cyclodextrin > or = alpha-cyclodextrin > or = beta-cyclodextrin. On the basis of yield pressure values and the Heckel plot profiles, all the cyclodextrins were highly prone to plastic deformation. Cyclodextrins showed time-dependent consolidation behaviour manifested as increased yield pressure with decreased contact time. A ratio was defined between the SRS of fast elastic recovery and total elastic recovery. The two materials with high ratios, HP-beta-cyclodextrin and beta-cyclodextrin, were especially prone to fast elastic recovery with increasing punch velocities; gamma-cyclodextrin and alpha-cyclodextrin had low values and were less prone. On the basis of this parameter it might be possible to categorize pharmaceutical materials according to capping tendency.

[Pancreatitis and inappropriate ADH secretion syndrome associated with amiodarone]. / Pancreatitis y síndrome de secreción inadecuada de ADH asociados a amiodarona.

We describe a case of hepatotoxicity, pancreatitis and inappropriate ADH secretion syndrome developed in a patient receiving chronic amiodarone treatment, not related to other causes. Hepatic toxicity is a well known condition. Inappropriate ADH secretion syndrome has not been described yet and there has been a single case-report of pancreatitis in the literature reviewed.

[Cardiac tamponade in a woman with primary hypothyroidism]. / Taponamiento cardiaco en una mujer con hipotiroidismo primario.

Pericardial effusion is not infrequent as a manifestation of hypothyroidism, however, cardiac tamponade is exceptional in these patients. We report a case of a female patient with cardiac tamponade that in the forward workshop was diagnosed of primary hypothyroidism. A brief presentation of clinical history is reported. The literature's review emphasizes the rarity of this case, the importance of the knowledge of triggering factors to establish a precious diagnosis and satisfactory clinical evolution with hormonal treatment without recurrences of the cardiac tamponade after pericardiocentesis is performed, although the resolution of the pericardial effusion is usually slow.

[An ACTH-secreting carcinoid tumor of the thymus. A report of a new case]. / Tumor carcinoide de timo secretor de ACTH. Presentación de un nuevo caso.

Carcinoid tumour of the thymus is a rare condition, with less than a hundred cases reported in the literature. Diagnosis is complex as they are usually asymptomatic. We describe a case of a severe Cushing syndrome developed in a 51-year-old man. The diagnosis of a thymic carcinoid was established. Three years ago, the patient was treated by surgical resection of an anterior mediastinal mass. A massive tumour dissemination was detected by MIBG and CT image techniques. Both techniques are currently considered useful for this kind of diagnosis. ACTH secretion was detected immunohistochemically. Although the treatment with SMS-201-995 octreotide was effective in controlling the clinical symptoms, the patient died three months later with extensive metastases. The carcinoid tumours of the thymus associated to Cushing syndrome are aggressive tumours and usually produce local and distant metastases.

Study of the compaction mechanisms of lactose-based direct compression excipients using indentation hardness and Heckel plots.

Indentation hardness of tablet surfaces has been used to determine the consolidation mechanisms of the lactose-based excipients Fast Flo Lactose, Ludipress, Cellactose and Tablettose. The Leuenberger equation has been modified to obtain values of compressibility and compactability by using a value of compactability obtained from a tablet at maximum applied force and by substituting deformation resistance by relative deformation resistance. Also, parameters obtained from plots of the Heckel tablet-indie and ejected-tablet methods were calculated in order to establish the comparative consolidation mechanisms in the lactose-based excipients under study. The possibility of using the absolute value of the difference between upper and lower surface hardnesses of the tablets made on an eccentric press is suggested as an alternative method to determine the comparative consolidation mechanisms of different substances.