Improving the solubility of pseudo-hydrophobic Alzheimer's Disease medicinal chemicals through co-crystal formulation.

Natural products are ligands and potential inhibitors of Alzheimer's disease (AD) tau. Dihydromyricetin (DHM) is a CNS active natural product. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols. Our research shows DHM becomes ionized at near-neutral pH allowing formulation of salts with transformed solubility. The MicroED co-crystal structure with trolamine reveals DHM salts as metastable solids with unlocked hydrogen bonding and a thermodynamic bent to solubilize in water. All salt formulations show better inhibitory activity against AD tau than the non-salt form, with efficacies correlating to enhanced solubilities. These results underscore the role of structural chemistry in guiding selection of solubilizing agents for chemical formulation. We propose DHM salts are appropriate formulations for research as dietary supplements to promote healthy aging by combating protein misfolding. Additionally, DHM is a suitable lead for medicinal chemistry and possible development of CNS pharmaceuticals.

Implications of equipment failure occurring during surgery.

INTRODUCTION: Few formal studies have been performed investigating the frequency of equipment failure during surgery. Surgeons are unable to operate without the plethora of instruments and equipment surrounding them in the operating theatre. As with any mechanical component, instruments and equipment are subject to time- and use-dependent degradation in their performance. Yet no formal requirements exist for the routine inspection or maintenance of instruments. Owing to this lack of information regarding equipment failure we undertook the first investigation of intraoperative equipment malfunction occurring during cardiac surgical procedures. METHODS: Over a 12-month period cardiac surgeons were required to report equipment malfunction during each procedure. Operating theatre equipment was divided into three categories broadly based on equipment portability and function: group 1, theatre infrastructure and components; group 2, large medical equipment; and group 3, surgical instruments. RESULTS: In a highly significant proportion of operations performed (92%) there was an issue with equipment. The most common issues occurred in group 3 with fine surgical instrument malfunctions; most commonly worn-out needle holders and blunt scissors. Theatre infrastructure and large medical equipment failures (groups 1 and 2) resulted in the cancellation of four cases. Some intraoperative instrument failures were potentially catastrophic. CONCLUSIONS: The incidence of equipment failure during cardiac surgery is unacceptably high. In some instances, cases were cancelled and revenue lost owing to equipment malfunction. A balance between the safety and quality of equipment and cost effectiveness is required. These findings suggest that surgical instruments warrant an annual compulsory inspection.

Retrosternal goitre assumed to be asthma causing asphyxia in pregnancy: case report and literature review.

The prevalence of asthma is high, but 'all that wheezes is not asthma'. We present the case of a 38-year-old pregnant woman who had acute severe ventilatory failure initially thought to be an exacerbation of asthma. This delayed the actual diagnosis of haemorrhagic enlargement of a goitre complicated by pre-eclampsia. We also perform a literature review of previous publications. This case highlights the goitrogenic effects of pregnancy and the associated risks of respiratory compromise.

Exfoliative immunocytology of cervical carcinoma.

Fluorescent antibody tracing was applied to exfoliative specimens from 456 women, who were also screened by cytology and partly by histopathology for carcinoma of the cervix. Fixed cervicovaginal smears were treated with autologous serum; the smears then were added labeled antihuman globulin antibody and observed for reactivity. A pattern of cytoplasmic fluorescence was observed in cases that were cytologically diagnosed as severe dysplasia, carcinoma in situ of the cervix, or in cases with positive reactions for malignant cells. Negative Papanicolaou smears appeared nonreactive. A probe into the immunoglobulin class of the antibody that reacted with dyskaryotic and abnormal cells revealed that IgA and IgG but not IgM were involved. The results indicate that a humoral immune response occurs and may be used diagnostically for a demonstration of cellular abnormality in premalignant and invasive cases of cervical carcinoma.

Iron-deficient medium for selective isolation and presumptive identification of enterococci.

An Enterococcus Selective Agar (ESA; basal medium plus 0.01% NaN3, pH 9.6, Fe ion-restricted) was applied to a direct, single-step, isolation and presumptive identification of enterococci from clinical urine. The ESA was examined as to rate of colony formation and selectivity together with two conventional culture media, Pfizer Selective Enterococcus Agar (PSE) and Phenyl Ethyl Alcohol Agar (PEA). Significant differences were observed in the rate of colony formation after 14, 17, and 20 hr of incubation at 35 degrees. The size of colonies on ESA was consistently larger than on the other two media. Biochemical testing showed that isolates from ESA conformed more closely to the definition of enterococci than isolates from either PSE or PEA. The improved selectivity of ESA was in large part due to the reduced presence of Fe ions. The medium offers advantages for an expeditious and accurate isolation of enterococcal pathogens.

Bronchogenic cyst imitating chronic asthma.

This case report demonstrates the dangers of assuming the accuracy of a neonatal diagnosis of asthma, that is not responsive to medical therapy, and highlights the value of CT imaging.

Development of a selective enterococcus medium based on manganese ion deficiency, sodium azide, and alkaline pH.

Rogosa broth, without its salt supplement and dissolved in deionized water, was adapted for the selective isolation and enumeration of enterococci. This medium supported good growth of enterococci, but it suppressed growth of other lactic acid bacteria. The sensitivity and specificity of the medium were tested after addition of various increasing concentrations of NaN(3) against known strains of enterococci and other bacteria. Many strains of Streptococcus faecium showed low azide tolerance; optimal growth was obtained at a concentration of 0.01% NaN(3), which totally or partially inhibited unrelated species of lactic acid bacteria. The selectivity of the medium was further increased by pH adjustment to 9.6. Carbonate and Tween 80 were added to overcome partial inhibition of enterococcal growth by the new combination of selective conditions. The final medium was evaluated in agar form in isolations from human and animal feces, polluted water, meat, and dairy products. Counts were obtained after 16 to 17 h of incubation at 37 C. The isolates satisfactorily conformed to the group characteristics of enterococci.

Difference between manganese ion requirements of pediococci and enterococci.

For maximal turbidity and dissimilatory activity, three strains of pediococci required the addition of Mn(2+) to Rogosa basal medium. Twenty-two strains of enterococci proved indifferent to this supplement.

Improved isolation and differentiation of enterococci in cheese.

Further documentation of an enterococcus selective differential (ESD) medium was obtained in isolations from eight different cheeses. An improved differentiation of tetrazolium salt (2, 3, 5-triphenyl tetrazolium hydrochloride [TTC])-reducing strains of Streptococcus faecalis from TTC-nonreducing or TTC-faintly-reducing Streptococcus faecium was attained. The sensitivity of the medium was evaluated in comparison with that of KF streptococcal, Pfizer selective enterococcus (PSE), the medium of Reinbold, Swern, and Hussong (RSH), and the medium of Saraswat, Clark, and Reinbold (SCR). Selective counts, rate of colony formation, and ease of isolation and differentiation of colonies were examined. The specificity of the medium was also investigated. ESD supported the fastest rate of growth and the maximum size of colonies; counts in this medium were in most cases possible with 17 h of incubation, whereas the other media required 24 to 48 h. A presumptive identification of 1,077 isolates by four biochemical tests disclosed that SCR, RSH, and ESD selected high, comparable percentages of strains that approximated most closely the typical description of enterococci (66, 60.1, and 58%, respectively). Low percentages (21.1 and 30.7%) were yielded by KF and PSE. The utility of ESD for a rapid, presumptive identification of enterococci was confirmed by serological and biochemical testing of color TTC-differentiated colonies isolated from 18 cheeses.