Virucidal efficacy of guanidine-free inactivants and rapid test buffers against SARS-CoV-2.

A pathogen inactivation step during collection or processing of clinical samples has the potential to reduce infectious risks associated with diagnostic procedures. It is essential that these inactivation methods are demonstrated to be effective, particularly for non-traditional inactivation reagents or for commercial products where the chemical composition is undisclosed. This study assessed inactivation effectiveness of twenty-four next-generation (guanidine-free) nucleic acid extraction lysis buffers and twelve rapid antigen test buffers against SARS-CoV-2, the causative agent of COVID-19. These data have significant safety implications for SARS-CoV-2 diagnostic testing and support the design and evidence-based risk assessment of these procedures.

High throughput testing of drug library substances and monoclonal antibodies for capacity to reduce formation of cystatin C dimers to identify candidates for treatment of hereditary cystatin C amyloid angiopathy.

OBJECTIVE: To establish a high-throughput system for testing the ability of drugs or monoclonal antibodies to reduce the in vitro formation of cystatin C dimers to identify substances potentially useful for treatment of patients with hereditary cystatin C amyloid angiopathy (HCCAA). METHODS: Various combinations of incubation temperature, time period, guanidinium chloride concentration and concentration of cystatin C monomers were tested in low-volume formats to induce dimer formation of recombinant cystatin C. The extent of dimerization was analysed by gel filtration chromatography and agarose gel electrophoresis. RESULTS: A high-throughput system based upon agarose gel electrophoresis was developed and used to test 1040 drugs in a clinical drug library for their capacity to reduce cystatin C dimer formation in vitro. Seventeen substances reducing dimer formation by more than 30% were identified. A similar system for testing the capacity of monoclonal antibodies against cystatin C to reduce the in vitro formation of cystatin C dimers was also developed and used to test a panel of 12 monoclonal antibodies. Seven antibodies reducing dimer formation by more than 30% were identified and the two most potent, Cyst28 and HCC3, reduced dimerization by 75 and 60%, respectively. CONCLUSION: We constructed a simple high-throughput system for testing the capacity of drugs and monoclonal antibodies to reduce the in vitro formation of cystatin C dimers and several candidates for treatment of HCCAA could be identified.

Tocólisis con clorhidrato de isoxuprina o nifedipina en la amenaza de parto pretérmino / Tocolysis with isoxuprine hydrochloride or nifedipine in preterm labor

Comparar la eficacia del clorhidrato de isoxuprina o la nifedipina en la tocólisis de la amenaza de parto pretérmino. Se seleccionaron 82 pacientes con edad gestacional entre 24 y 34 semanas y diagnóstico de amenaza de parto pretérmino. Las pacientes se dividieron al azar en 2 grupos para recibir clorhidrato de isoxuprina (grupo A) o nifedipina (grupo B). Se determinaron el tiempo de cese de las contracciones, tensión arterial materna, concentraciones de glucosa y efectos adversos maternos. Maternidad "Dr. Nerio Belloso", Hospital Central "Dr. Urquinaona", Maracaibo. Estado Zulia. Se logró una tocólisis efectiva en las primeras 24 horas en 61,0 por ciento y 70,7 por ciento de las pacientes del grupo A y B, respectivamente (P = ns). Después de 7 días de tratamiento, 36,6 por ciento de las pacientes en el grupo A y 31,7 por ciento de las pacientes en el grupo B aun permanecían sin contracciones (P = ns). Se logró un retraso del parto hasta las 34 semanas o más en 26,8 por ciento y 29,3 por ciento de las pacientes de los grupos A y B, respectivamente. En el grupo de pacientes tratadas con clorhidrato de isoxuprina se observó un aumento significativo de las concentraciones séricas de glucosa (P < 0,001). Los efectos adversos maternos fueron significativamente más frecuentes en el grupo de clorhidrato de isoxuprina después de 2 y 24 horas de tratamiento (P < 0,05). La nifedipina es igual de efectiva que el clorhidrato de isoxuprina en la tocólisis de la amenaza de parto pretérmino y produce menos efectos adversos

To compare the efficacy of isoxuprine clorhidrate or nifedipine in tocolysis of threatened preterm labor. 82 patients with a gestational age between 24 and 34 weeks and threatened preterm labor diagnosis were selected. Patients were randomly divided in 2 groups to receive isoxuprine clorhidrate (group A) or nifedipine (group B). Time of cease of contractions, maternal blood pressure, glucose concentrations and maternal adverse effects were determined. Maternidad "Dr. Nerio Belloso", Hospital Central "Dr. Urquinaona", Maracaibo. Estado Zulia. An effective tocolysis was obtained within 24 hours in 61.0 percent and 70.7 percent for patients in group A and B, respectively (P = ns). After 7 days of treatment, 36.6 percent of patients in group A and 31,7 percent of patients in group B were still without contractions (P = ns). A delay in labor till 34 weeks or more was made in 26.8. percent and 29.3 percent of patients in group A and B, respectively. In the group of patients treated with isoxuprine clorhidrate a significant raise of glucose concentrations was observed (P < 0.001). Maternal adverse effects were significant more frequent in isoxuprine clorhidrate group after 2 and 24 hours of treatment (P < 0,05). Nifedipine has a similar effectivity than isoxuprine clorhidrate for tocolysis in threatened preterm labor and produces less adverse effects

Stability enhancement of cytochrome c through heme deprotonation and mutations.

The chemical denaturation of Pseudomonas aeruginosa cytochrome c(551) variants was examined at pH 5.0 and 3.6. All variants were stabilized at both pHs compared with the wild-type. Remarkably, the variants carrying the F34Y and/or E43Y mutations were more stabilized than those having the F7A/V13M or V78I ones at pH 5.0 compared with at pH 3.6 by ~3.0-4.6 kJ/mol. Structural analyses predicted that the side chains of introduced Tyr-34 and Tyr-43 become hydrogen donors for the hydrogen bond formation with heme 17-propionate at pH 5.0, but less efficiently at pH 3.6, because the propionate is deprotonated at the higher pH. Our results provide an insight into a stabilization strategy for heme proteins involving variation of the heme electronic state and introduction of appropriate mutations.

[Comparative evaluation of the safety of poly- and and oligoguanidines].

The antimicrobial activity and microenvironmental safety of poly- and oligoguanidine antiseptics were compared. E. coli and St. aureus test strains were found to be more sensitive to chlorohexidine bigluconate (CHB) upon a long (24 hour) exposure and to polyhexamethylene guanidine derivatives on short (30-second) contact. It is concluded that unlike polyguanidine antiseptics, CHB is more ecologically dangerous; when used for rapid disinfection, it can provoke impairment in the microenvironmental balance outside the area of application. The findings show it expedient to assess the microenvironmental safety of antimicrobial agents in order to prevent ecological catastrophes.