scholarly journals Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study

2021 ◽  
Vol 0 ◽  
pp. 1-6
Author(s):  
Charussri Leeyaphan ◽  
Bordeesuda Suiwongsa ◽  
Phojana Komesmuneeborirak ◽  
Rungsima Kiratiwongwan ◽  
Supisara Wongdama ◽  
...  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Amphotericin B ◽  
Small Sample Size ◽  
Fungal Species ◽  
Small Sample ◽  
Controlled Study ◽  
Mycological Cure ◽  
Accurate Identification

Background: Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited. Objectives: We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control. Methods: This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated. Results: Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed. Limitations: The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study. Conclusion: Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity.

Probing the ultrastructure of the mitotic and meiotic spindle in eggs: An expeditious approach based on semi-thin (0.25 μm) serial sections

1983 ◽  
Vol 41 ◽  
pp. 552-555
Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder
Keyword(s):  
Small Sample Size ◽  
Small Sample ◽  
Meiotic Spindle ◽  
Serial Sections ◽  
Mitotic Apparatus ◽  
Thin Sections ◽  
Cell Cycles ◽  
Ultrastructural Studies

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).

scholarly journals In vivo assessment of a single adenine mutation in 5′UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Minati Choudhury ◽  
Sakshi Dhingra Batra ◽  
Kriti Sikri ◽  
Anushree Gupta
Keyword(s):  
Pulmonary Hypertension ◽  
Congenital Heart ◽  
Small Sample Size ◽  
Small Sample ◽  
Severe Pulmonary Hypertension ◽  
Endothelin 1 ◽  
Circulating Levels ◽  
In Vivo Assessment

Abstract Objective Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 ‘A’, adenine insertion variant in 5′UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. Results The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 ‘A’ insertion variant in 5′UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted ‘A’ allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

scholarly journals Development of AOSpine BOnE (Bone Osteobiologics and Evidence) Classification

2019 ◽  
Vol 10 (7) ◽  
pp. 871-874 ◽  
Author(s):  
Jeffrey C. Wang ◽  
S. Tim Yoon ◽  
Darrel S. Brodke ◽  
Jong-Beom Park ◽  
Patrick Hsieh ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Small Sample ◽  
In Vitro Studies ◽  
Level Of Evidence ◽  
Knowledge Forum ◽  
Levels Of Evidence ◽  
Published Evidence ◽  
Patient Reported

Study Design: Classification development. Objectives: The aim of our study was to develop a 3-tier classification for the levels of evidence for osteobiologics and provide a description of the principles by which osteobiologics can be evaluated. BOnE (Bone Osteobiologics and Evidence) classification evaluates each osteobiologic based on the available evidence, and if the published evidence is based on clinical, in vivo or in vitro studies. Methods: The process of establishing the BOnE classification included 5 face-to-face meetings and 2 web calls among members of the AOSpine Knowledge Forum Degenerative. Results: The 3 levels of evidence were determined based on the type of data on osteobiologics: level A for human studies, level B for animal studies, and level C for in vitro studies, with level A being the highest level of evidence. Each level was organized into 4 subgroups (eg, A1, A2, A3, and A4). Conclusions: The use and the variety of osteobiologics for spine fusion has dramatically increased over the past few decades; however, literature on their effectiveness is inconclusive. Several prior systematic reviews developed by AOSpine Knowledge Forum Degenerative reported low level of evidence primarily due to the high risk of bias, small sample size, lack of control groups, and limited patient-reported outcomes. BOnE classification will provide a universal platform for research studies and journal publications to classify a new or an existing product and will allow for creating decision-making algorithms for surgical planning.

In Vivo Susceptibility of Cryptococcus neoformans to Hamycin, Amphotericin B, and 5-Fluorocytosine

1970 ◽  
Vol 1 (1) ◽  
pp. 128-134
Author(s):  
Smith Shadomy ◽  
H. Jean Shadomy ◽  
J. P. Utz
Keyword(s):  
Dimethyl Sulfoxide ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Effective Drug ◽  
Toxic Compound ◽  
Experimental Infections ◽  
Gastric Intubation

Previous investigations have shown that hamycin is 5 to 10 times more active in vitro than amphotericin B against Cryptococcus neoformans , whereas 5-fluorocytosine is approximately 15 times less active. Present studies are concerned with a comparison of these drugs in vivo. Three strains of C. neoformans which varied in both their virulence for mice and their susceptibilities to the antifungal agents were studied. Acute experimental infections were established in mice by using inocula containing approximately 4 × 10 6 cells. The mice were treated by gastric intubation for 28 days; daily dosages of the three drugs ranged from 12.5 to 250 mg/kg. The polyenes were suspended in 5% dimethyl sulfoxide, whereas 5-fluorocytosine was suspended in saline. Amphotericin B was the most effective drug, with almost complete absence of toxic deaths in control mice and increased survival in mice infected with two of the three strains and treated with 25 mg/kg per day or more. 5-Fluorocytosine was nontoxic but provided protection against only one strain. Hamycin was both the least effective and the most toxic compound, providing only slight protection at doses of 12.5 or 25 mg/kg per day and causing toxic deaths in over 50% of uninfected mice at doses above 25 mg/kg per day.

Serum α-Inhibin Levels in Polycystic Ovary Syndrome: Relationship to the Serum Androstenedione Level1

1997 ◽  
Vol 82 (6) ◽  
pp. 1939-1943
Author(s):  
Pascal Pigny ◽  
Rachel Desailloud ◽  
Christine Cortet-Rudelli ◽  
Alain Duhamel ◽  
Delphine Deroubaix-Allard ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Small Sample Size ◽  
Small Sample ◽  
Molecular Forms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovary Syndrome

Abstract To date, only one study has demonstrated increased serum inhibin levels in women with polycystic ovary syndrome (PCOS). Moreover, no relationship between serum inhibin and either FSH or androgen levels has been noted. This lack of data could be due to 1) the heterogeneity of PCOS and the small sample size of previous studies, and/or 2) the complexity of circulating inhibin molecular forms, which hinders the precise evaluation of bioactive inhibin. In the present study,α -inhibin levels were assayed in the serum of 61 healthy women and 72 PCOS patients by means of an α-α enzyme-linked immunosorbent assay. Serum α-inhibin levels together with LH and androstenedione (A) levels were significantly increased in PCOS women (mean ± sd, 1.45 ± 0.55 vs. 0.94 ± 0.36 U/mL in controls; P < 0.001). Moreover, simple and partial regression analysis demonstrated that serum A levels were positively and independently correlated to serum α-inhibin (r = 0.32; P < 0.01) and LH levels (r = 0.48; P < 0.001) in PCOS. The respective influences of α-inhibin and LH on A variability were 20% and 80%, as determined by multiple regression analysis. In conclusion, in agreement with recent in vitro data, our in vivo results argue for a role of inhibin in the hyperandrogenism of PCOS together with, but independently from, that of LH. Further studies are needed to determine whether this effect is produced by inhibin A and/or B.

A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

2020 ◽  
Vol 36 (2) ◽  
pp. 95-106
Author(s):  
Agnieszka M. Piróg-Balcerzak ◽  
Anna K. Bażyńska ◽  
Katarzyna Biernacka ◽  
Joanna Brągoszewska ◽  
Lidia Popek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Anorexia Nervosa ◽  
Polyunsaturated Fatty Acids ◽  
Small Sample Size ◽  
Small Sample ◽  
Female Adolescent ◽  
Eating Attitude ◽  
Controlled Study ◽  
Omega 3 ◽  
Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

scholarly journals 1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S800
Author(s):  
Nerea Irusta ◽  
Ana Vega ◽  
Yoichiro Natori ◽  
Lilian M Abbo ◽  
Lilian M Abbo ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Small Sample ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
Secondary Outcomes ◽  
Related Mortality

Abstract Background In-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI. Methods IRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if < 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach. Results A total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075). Table 1: Patient Characteristics Table 2. Primary and Secondary Outcomes Conclusion We did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings. Disclosures All Authors: No reported disclosures

scholarly journals Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

2015 ◽  
Vol 59 (5) ◽  
pp. 2479-2487 ◽  
Author(s):  
Keerti Jain ◽  
Ashwni Kumar Verma ◽  
Prabhat Ranjan Mishra ◽  
Narendra Kumar Jain
Keyword(s):  
Drug Release ◽  
Amphotericin B ◽  
Human Erythrocytes ◽  
Antileishmanial Activity ◽  
Cell Uptake ◽  
Antiparasitic Activity ◽  
Content Type ◽  
Drug Localization

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.

scholarly journals EJE Prize 2013: Regulation of aldosterone secretion: from physiology to disease

2013 ◽  
Vol 168 (6) ◽  
pp. R85-R93 ◽  
Author(s):  
Felix Beuschlein
Keyword(s):  
High Throughput Sequencing ◽  
Secondary Hypertension ◽  
Small Sample ◽  
Cellular Systems ◽  
Common Disease ◽  
Aldosterone Secretion ◽  
Technical Developments ◽  
Starting Point

Arterial hypertension is a major cardiovascular risk factor that affects between 10 and 40% of the population in industrialized countries. Primary aldosteronism (PA) is the most common form of secondary hypertension with an estimated prevalence of around 10% in referral centers and 4% in a primary care setting. Despite its high prevalence until recently, the underlying genetic and molecular basis of this common disease had remained largely obscure. Over the past decade, a number of insights have been achieved that have relied onin vitrocellular systems, wild-type and genetically modifiedin vivomodels, as well as clinical studies in well-characterized patient populations. This progress has been made possible by a number of independent technical developments including that of specific hormone assays that allow measurement in small sample volumes as well as genetic techniques that enable high-throughput sequencing of a large number of samples. Furthermore, animal models have provided important insights into the physiology of aldosterone regulation that have served as a starting point for investigation of mechanisms involved in autonomous aldosterone secretion. Finally, national and international networks that have built up registries and biobanks have been instrumental in fostering translational research endeavors in PA. Therefore, it is to be expected that in the near future, further pathophysiological mechanisms that result in autonomous aldosterone secretion will be unraveled.

scholarly journals Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major

2006 ◽  
Vol 396 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Chrysoula Panethymitaki ◽  
Paul W. Bowyer ◽  
Helen P. Price ◽  
Robin J. Leatherbarrow ◽  
Katherine A. Brown ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Homo Sapiens ◽  
Selective Inhibition ◽  
Fungal Species ◽  
Chemotherapeutic Agents ◽  
Human Pathogens ◽  
Ic50 Values

The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC50 values of <1 μM and are also active against mammalian parasite stages, with ED50 (the effective dose that allows 50% cell growth) values of 16–66 μM and low toxicity to murine macrophages. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against infectious diseases including African sleeping sickness and Nagana.

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