Hydrophobic surface protein masking by the opportunistic fungal pathogen Candida albicans.

Ultrastructural and biochemical analyses of hydrophobic and hydrophilic yeast cell surface proteins of Candida albicans were performed. Hydrophobic and hydrophilic yeast cells were obtained by growth at 23 and 37 degrees C, respectively. In addition, hydrophilic yeast cells were converted to surface hydrophobicity by treatment with tunicamycin and dithiothreitol. When freeze-etched cells were examined, the temperature-induced hydrophilic cells had long (0.198 micron), compact, evenly distributed fibrils while temperature-induced hydrophobic cells had short (0.085 micron), blunt fibrils. Hydrophobic microsphere attachment to the hydrophobic cells occurred at the basement of and within the short fibril layer. Dithiothreitol-induced hydrophobic cells had the long fibrils removed; tunicamycin-induced hydrophobic cells retained some of the long fibrils, but the fibrils were less compact and more aggregated than the untreated controls. These results suggest that the long fibrils prevent hydrophobic microsphere attachment to the hydrophobic area of the cell surface. This was confirmed by assessing the hydrophobic avidity of hydrophobic yeast cell populations differing in fibril density and arrangement. 125I-labelled surface proteins from hydrophobic and hydrophilic cells were compared after separation by hydrophobic interaction chromatography-high-performance liquid chromatography and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The yeast cell populations had hydrophilic proteins of similar molecular masses (greater than 200 kDa), but the hydrophilic cells possessed at least two additional proteins (ca. 63 and 69 to 71 kDa). Hydrophobic surface proteins appeared to be similar. However, the amount of total radiolabelled hydrophobic proteins was approximately 10-fold higher for the hydrophobic cells than for the hydrophilic cells. This result agrees with the ultrastructural observations which showed that yeast cell surface hydrophobic proteins are masked by hydrophilic high-molecular-mass surface fibrils. Taken together, the data indicate that yeast cell hydrophobicity is not determined by differences in surface hydrophobic proteins but by the presence of hydrophilic, surface fibrils.     

Role of yeast cell growth temperature on Candida albicans virulence in mice.

Previous studies have suggested that yeast cell growth temperature may influence the relative virulence of the opportunistic dimorphic fungus Candida albicans. To test this possibility, mice were challenged with C. albicans yeast cells which were grown at either room temperature or 37 degrees C, and their survival was monitored daily. Mice which received room temperature-grown cells died faster. The interaction of glycogen-elicited polymorphonucleated neutrophils (PMNs) with C. albicans yeast cells grown at the two temperatures was examined, because PMNs have been shown to have a critical role in preventing development of candidiasis in normal individuals. In the absence of serum (i.e., nonopsonic conditions), more PMNs conjugated and engulfed C. albicans cells grown at room temperature than those grown at 37 degrees C. However, PMNs were less able to kill cells grown at room temperature than cells grown at 37 degrees C. Cells grown at room temperature also produced abundant germ tubes after engulfment and were thus more likely to escape killing by phagocytes. These results suggest that cells grown at room temperature are more virulent because they are less likely to be killed by phagocytes and are more likely to disseminate. The possibility that expression of cell surface hydrophobicity is involved in these events is discussed.     

Capdepont dysplasia and vertical excess of the lower half of the face. Genetic syndrome or fortuitous association?

The study of an Algerian family revealed that four of the seven children presented dentinogenesis imperfecta associated with an anomaly of the facial skeleton (maxillary hypoplasia, anterior expansion of skeletal origin due to widening of the angle of the gonion). This type of association and its very unusual type of transmission (no doubt recessive) leads to a discussion of genetic mechanisms of these syndromes.     

Effects of calcisorb on fecal bile acids and fatty acids in human volunteers

The intake of calcium (Ca) is negatively associated with colorectal cancer (crc) risk. The aim of this study was to investigate in a double-blind, placebo-controlled trial, the effects of the Ca-binder Calcisorb, which is given to kidney stone patients with hypercalciuria type I, on risk factors for crc risk, bile acids (BA), and long-chain fatty acids (LCFA) in fecal water. Results show that the concentration of BA and LCFA in fecal water did not change, although the urinary excretion of Ca and magnesium (Mg) and the concentration of Ca and magnesium in fecal water decreased. The daily excretion of BA and LCFA acids decreased significantly (p < 0.05) during the Calcisorb period. In conclusion, binding dietary Ca and Mg with Calcisorb from a diet with a relatively low amount of fat does not enhance the solubility of BA and LCFA in fecal water.     

Provision of clinical pharmacy services during the COVID-19 pandemic: Experiences of pharmacists from 16 European countries

BackgroundThe pharmacy profession has an important role in the frontline healthcare response to COVID-19 across all settings.ObjectiveThis study sought to explore the views and experiences of clinical pharmacists in relation to the provision of clinical pharmacy services during COVID-19.MethodsSemi-structured qualitative interviews were conducted with pharmacists working in clinical roles in healthcare settings across Europe. Participants were recruited through professional organisations of clinical and hospitals pharmacists combined with a snowballing technique. The Pharmacy Emergency Preparedness and Response Framework and Disaster Preparedness Framework for pharmacy services were used to generate data which were analysed using the thematic framework method.ResultsTwenty-two participants from 16 European countries described a range of measures to protect patients, public and healthcare staff against virus transmission including developing and disseminating educational materials. Most described their involvement in aspects of evidence provision such as facilitating clinical trials, gathering and appraising evidence and disseminating clinical information. Many hospital-based pharmacists were reassigned to new roles such as intensive care. Routine clinical services were extensively interrupted and remote forms of communication were used. Most were motivated by a strong sense of professionalism to continue delivering services. A number of facilitators and barriers to prevention, preparedness and response actions were identified which related to uptake of new roles, recognition of pharmacists roles in the healthcare team, information gathering, communication with patients and healthcare professionals, and provision of routine clinical services.ConclusionsParticipants in this multinational qualitative study described a range of service adaptations and adoption of novel roles to prevent and mitigate the public health impact of the pandemic. The study findings may help to inform governments, public health agencies and healthcare systems in harnessing ongoing service provision and adapt to any future interruptions.     

Pharmacists’ involvement in COVID-19 vaccination across Europe: a situational analysis of current practice and policy

International Journal of Clinical Pharmacy - One year since the emergence of the COVID-19 pandemic, rapid response measures have been implemented internationally to mitigate the spread of the...     

CALCIFICATION OF THE BREAST FOLLOWING A TYPHOID ABSCESS

1. In a patient with typhoid fever, who had taken, during eleven days, 132 grammes of lactate of calcium by the mouth, as well as 5 grammes of chloride of calcium subcutaneously, there developed, eleven days after the subcutaneous infusion, a large abscess of the breast from which Bacillus typhosus and Staphylococcus aureus were obtained on culture. The abscess was opened and the wound packed with iodoform gauze. Eleven days later a deposit of calcium appeared in the granulation tissue bordering the wound. This rapidly increased until the rim of the opening and the lining granulation tissue were converted into a hard, calcareous mass. A number of nodules of an apparently similar character appeared in other parts of the breast. 2. A month later the iodoform packing was removed and the patient was put on a carbohydrate free diet. This was continued for twenty-four of the next thirty-six days. Under this treatment the abscess almost entirely healed with complete disappearance of the deposit of calcium. 3. Studies of the intake and output of calcium showed that, during three days under a diet of milk and eggs there was a material calcium retention (^I.346 grammes) : (b) That during two periods amounting to three weeks in all, under a carbohydrate free diet, there was an excess of Ca elimination over the intake of 3.672 grammes, (c) That during ten days following the last carbohydrate free period, under a normal diet, there was a retention of calcium amounting to 0.602 gramme. 4. The disappearance of calcium from the breast was associated in time with the carbohydrate free diet and the excessive elimination of calcium. 3. Under the carbohydrate free diet acetone and diacetic acid appeared on two occasions in the urine, but were not accompanied by any increase in the elimination of calcium. 6. With regard to the cause of the calcification, we cannot speak with certainty. The remarkable association of the deposition of calcium at the seat of an injection of calcium chloride in an individual who had been receiving large quantities of lactate of calcium by the mouth—a deposition occurring in tissues which were in direct connection with or in the immediate neighborhood of a dressing containing iodoform, a poison which in certain animals produces degenerative changes in the kidneys and liver which are peculiarly prone to calcification, is striking and worthy of note. 7. In how far the decalcification of the affected area may have been due to the carbohydrate free regime with the consequent excess in calcium elimination, it is impossible, on the basis of a single case, to say. The coincidence in time of the disappearance of calcium from the breast with this treatment is, however, remarkable and extremely suggestive.     

Formation of dysfunctional high-density lipoprotein by myeloperoxidase

Recent studies identify the presence of high-density lipoprotein (HDL) particles in patients with cardiovascular disease, which are "dysfunctional," lacking in typical atheroprotective properties, and promoting proinflammatory effects. The mechanisms for generating dysfunctional HDL have been unclear. New evidence points to a role for myeloperoxidase (MPO)-generated oxidants as participants in rendering HDL dysfunctional within human atherosclerotic plaque. Myeloperoxidase was recently shown to bind to HDL within human atherosclerotic lesions, and biophysical studies reveal MPO binding occurs via specific interactions with apolipoprotein (apo) A-I, the predominant protein of HDL. This likely facilitates the observed selective targeting of apoA-I for site-specific chlorination and nitration by MPO-generated reactive oxidants in vivo. One apparent consequence of MPO-catalyzed apoA-I oxidation includes the functional impairment of the ability of HDL to promote cellular cholesterol efflux via the adenosine triphosphate binding cassette-1 transport system. Myeloperoxidase-mediated loss of the atheroprotective functional properties of HDL may thus provide a novel mechanism linking inflammation and oxidative stress to the pathogenesis of atherosclerosis.