Compactibility of agglomerated mixtures of calcium carbonate and microcrystalline cellulose

The tablet tensile strength (T) of agglomerated mixtures of microcrystalline cellulose-Avicel PH 102 (MC), calcium carbonate (CC) and polyvinylpyrrolidone (Povidone, PVP), lubricated with magnesium stearate (MS), and formed under a compaction pressure (P(c)) ranging up to 618MPa has been determined. The compactibility was defined through: ln(-ln(1-T/T(max)))=Slope x lnP(c)+Intercept. MC/CC mixtures added of an agglutinant, before and after lubrication, show an important positive effect on their tablet tensile strength compared to a lineal relationship. This positive effect becomes smaller with decreasing compaction pressures. By different mixing methods, the higher the mixing efficiency the higher the compactibility, following the order: spray-dried>wet massing>tumble mixing. The compactibility of MC/CC/PVP spray-dried mixtures with calcium carbonate content from 20 to 60% was equal to or greater than that of pure microcrystalline cellulose. After lubrication with 2% MS the compactibility decreased, only the mixture with the maximal tablet tensile strength attained the tensile strength of pure microcrystalline cellulose. The presence of the binder, the lubricant and higher compaction pressures allow the accommodation of higher calcium carbonate proportions in the mixtures, at the maximal tablet tensile strength of the series. The lubricant decreases in a greater extent the compactibility of mixtures with a continuous phase of MC/PVP than that of CC/PVP. This is attributed to the plastic behavior of the MC/PVP continuous phase compared to a calcium carbonate continuous phase able to disrupt the Povidone and the possible lubricant coatings allowing a stronger interparticle interaction.     

Current Evidence for Stereotactic Body Radiotherapy in Lung Metastases

Lung metastases are the second most common malignant neoplasms of the lung. It is estimated that 20–54% of cancer patients have lung metastases at some point during their disease course, and at least 50% of cancer-related deaths occur at this stage. Lung metastases are widely accepted to be oligometastatic when five lesions or less occur separately in up to three organs. Stereotactic body radiation therapy (SBRT) is a noninvasive, safe, and effective treatment for metastatic lung disease in carefully selected patients. There is no current consensus on the ideal dose and fractionation for SBRT in lung metastases, and it is the subject of study in ongoing clinical trials, which examines different locations in the lung (central and peripheral). This review discusses current indications, fractionations, challenges, and technical requirements for lung SBRT.     

Fecal Mycobiota Combined With Host Immune Factors Distinguish Clostridioides difficile Infection From Asymptomatic Carriage

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Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5- 15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti- inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints.      

In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells

Recently, the ligand for c-mpl has been identified and cloned. Initial studies of this molecule indicate that it is the platelet regulatory factor, thrombopoietin (TPO). Previous work has indicated that c-mpl is expressed in very immature hematopoietic precursors and thus raised the possibility that TPO may act directly on the hematopoietic stem cell. Therefore, in these studies, we investigate the effects of TPO on hematopoietic stem cell populations isolated from the murine fetal liver and bone marrow. Cocultivation of stem cells with fetal liver stroma give rise to multilineage expansion of the stem cells but with little or no megakaryocytopoiesis. Addition of TPO to these cocultures gives significant megakaryocyte production. This production is enhanced in combination with Kit ligand or interleukin-3. The addition of TPO to stem cell suspension cultures produces a dynamic thrombopoietic system in which stem cells undergo differentiation to produce megakaryocytes and proplatelets. These experiments show that the megakaryocytopoietic and thrombopoietic activities of TPO are initiated at the level of an early progenitor cell or upon the hematopoietic stem cell.     

Preliminary Results of Non‐Surgical Periodontal Treatment in Patients With Breast Cancer Undergoing Chemotherapy

Background: Although priority is often given to treat the cancer itself, focus should also be directed to prevention and improvement of oral complications that may occur as a result of cancer and/or its treatment. This study compares periodontal treatment results in healthy patients and patients with breast cancer undergoing chemotherapy by monitoring clinical conditions and C‐reactive‐protein (CRP) levels. Methods: Thirty‐five participants were allocated to one of two groups: patients with periodontitis (P) (n = 18) and patients with breast cancer and periodontitis (CAN/P) (n = 17). The following clinical parameters were assessed at baseline and 45, 90, and 180 days after non‐surgical periodontal treatment (NSPT): 1) probing depth (PD); 2) clinical attachment level (CAL); 3) plaque index (PI); 4) gingival index (GI); 5) CRP; and 6) complete blood count. Clinical parameters and CRP levels were statistically analyzed. Results: P and CAN/P groups presented a statistically significant decrease in PD after NSPT at 45, 90, and 180 days compared with baseline (P <0.05). There was a CAL gain in the P group and a significant reduction in PI and GI at 45, 90, and 180 days for both groups (P <0.05). At 180 days after NSPT treatment, the CAN/P group showed a higher number of residual pockets (P <0.05) compared with the P group (46.48 ± 26.80 and 7.58 ± 7.40, respectively). The P group demonstrated a significant reduction in CRP levels at 45 and 180 days after NSPT compared with baseline (P <0.05), whereas this reduction was not observed in the CAN/P group. Conclusion: Patients with breast cancer who were undergoing chemotherapy responded to periodontal non‐surgical therapy, although with less favorable results than patients with periodontitis without cancer, and may require additional or adjunctive periodontal treatments.     

Neutralization of heparin activity by neutrophil lactoferrin

Lactoferrin is a prominent component of neutrophil secondary granules, and its blood concentration is increased in certain inflammatory diseases. In contrast to the well-described biochemical characterization of lactoferrin as an iron-binding protein, its physiologic role in the regulation of inflammation and other host defense mechanisms is unclear. In this report, we provide evidence that lactoferrin has a potent heparin-neutralizing activity during thrombin inhibition by the serine proteinase inhibitors (serpins) antithrombin and heparin co-factor II. Activated neutrophil supernatant, which contains lactoferrin and other heparin-binding proteins, could neutralize the heparin-dependent antithrombin-thrombin inhibition reaction. The addition of lactoferrin to plasma corrected the heparin- induced prolongation of blood plasma coagulation as measured by the activated partial thromboplastin time (aPTT). Treatment of whole blood with specific inflammatory mediators, fMLP, lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) increased the concentration of both plasma lactoferrin and platelet factor 4 while inhibiting the blood anticoagulant activity of heparin as measured by the aPTT. These results suggest that the prothrombotic sequelae of some inflammatory processes may be partly due to various agonists that release neutrophil lactoferrin, which can then neutralize glycosaminoglycan-dependent serpin-thrombin inhibition reactions.     

Measurement of ploidy distribution in megakaryocyte colonies obtained from culture: with studies of the effects of thrombocytopenia

Microdensitometric measurement of the DNA content of individual megakaryocytes was performed using megakaryocyte colonies obtained following culture, in soft agar, of hematopoietic cells from C57BL/6J mice. Two types of colonies were detected. After 7 days of culture, the big cell type contained 16 /+- 2.3 acetylcholinesterase (AChE) positive cells/colony, with a mean ploidy level of 16.8 /+- 0.8/cell and the ploidy distribution characteristic of recognizable megakaryocytes in bone marrow. The heterogeneous type contained 44 /+- 9.6 cells/colony (some of which were AChE negative), with a mean ploidy level of 6.8 /+- 0.7/cell. The ploidy distribution of heterogeneous colonies differed markedly from big cell colonies, with preponderance of 2N and 4N cells. Colony-forming cells, obtained 4-5 days after induction of acute thrombocytopenia, gave big cell colonies with a marked increase in DNA content. Mean ploidy level increased to 21.5 /%- 1.8/cell; the frequency of 32N cells increased from 17% to 30% and 64N cells from 0% to 6%. This is the pattern of change observed in bone marrow, in vivo, 24 to 48 hr after induction of acute thrombocytopenia. The number of cells/colony did not increase. In contrast, acute thrombocytopenia did not alter the ploidy of heterogeneous colonies. The different responses to the stimulus of acute thrombocytopenia suggest that there are at least two types of Meg-CFC. The delayed appearance of altered Meg-CFC that produced big cell colonies indicates that the pool of stem cells, from which committed megakaryocyte precursors are derived, may respond indirectly to the stimulus of platelet depletion.     

A fatal case of AIDS-defining meningoencephalitis by C. Neoformans,sensitive to antifungal therapy

Cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in HIV-infected patients. Diagnosis is based on tests for cryptoccocal antigen in serum and cerebrospinal fluid, and on culture of the organism. We present a case of AIDS-related cryptococcal meningoencephalitis unresponsive to antifungal combination therapy, despite of evidence of fungal susceptibility in vitro. Significant decreases in cryptococcal antigen titers in serum and cerebrospinal fluid did not correlate with progress in disease and fatal outcome.