Thermotolerance of Histoplasma capsulatum at 40 °C predominates among clinical isolates from different Latin American regions

ABSTRACT The yeast phase of 22 Histoplasma capsulatum clinical isolates from Mexico, Argentina, Colombia, and Guatemala and three reference strains, one from Panama and two from the United States of America (USA), were screened for thermosensitivity characteristics using different analyses. Growth curves at 0, 3, 6, 12, 24, and 30 h of incubation at 37 and 40 °C, the growth inhibition percentage at 40 °C, and the doubling time at 37 and 40 °C were determined for all yeasts studied. Most of the isolates examined exhibited thermotolerant phenotypes at 40 °C, whereas a thermosensitive phenotype at 40 °C was only detected in the Downs reference strain from the USA. Growth inhibition values lower than 33.8% supported the predominance of the thermotolerant phenotype at 40 °C. The doubling time means found for the different isolates were 5.14 h ± 1.47 h at 37 °C and 5.55 h ± 1.87 h at 40 °C. This is the first report to underscore the predominance of thermotolerant and delayed doubling time phenotypes in H. capsulatum clinical isolates from different regions of Latin America.

Protection Provided by a Gabexate Mesylate Thermo-Sensitive In Situ Gel for Rats with Grade III Pancreatic Trauma

BACKGROUND/AIMS: This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. METHODS: A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. CONCLUSIONS: GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.

Core-crosslinked poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(ε-caprolactone)micelles for paclitaxel thermo-sensitive controlled release behaviors / 中国组织工程研究

BACKGROUND: Polymer micelles is a new type of drug carriers developed in recent years,with a wide range of carrying drugs,structural stability,excellent tissue permeability,long residence of drugs in vivo,and effective reaching the target.The performances of intelligent targeting and decreasing the initial burst release have become the focus of recent researches.OBJECTIVE: To obtain an intelligent targeting drug carrier of low critical solution temperature(LCST)at 40℃,to change drug release behavior through the changes of temperature,and to further improve the stability and drug release behavior of the micelles by core-crosslinking.METHODS: By radical polymerization of N-isopropylacrylamide(NIPAAm)and N,N-dimethylacrylamide(DMAAm),hydroxyl terminated poly(N-isopropylacrylamide-co-N,N-dimethyl acrylamide)[P(NIPAAm-co-DMAAm)]was synthesized.Molecular weight and LCST of P(NIPAAm-co-DMAAm)were regulated by adjusting the mercaptoethanol and monomer ratio,as well as the ratio of NIPAAm and DMAAm,Amphiphilic block copolymer P(NIPAAm-CO-DMAAm)-b-PCL was prepared via bulk ring-opening polymerization of ε-caprolactone by using the end hydroxyl group of P(NIPAAm-co-DMAAm)as initiator and stannous octoate as catalyst.The block copolymer reacted with acryloyl chloride to obtain amphiphilic block copolymers with unsaturated double bonds at the terminal.Drug loaded nano-micelles with different nuclear cross-linked degrees were prepared by dialysis method,and its release behavior was investigated.RESULTS AND CONCLUSION: Amphiphilic block copolymers,with the LCST of 42℃,were obtained with hydroxyl or acryloyl endgroup.By blending them at different ratios,thermo-sensitive drug-loaded nano-micelles with different core-cresslinking degrees were prepared.The drug release rate was faster at 43℃ than at 37℃.With the core-crosslinking degrees increasing,the release of paclitaxel gradually slowed.The results suggest that the drug release rate from micelles prepared from thermo-sensitive P(NIPAAm-co-DMAAm)-b-PCL can be regulated by the degree of cross-linking.

Effects of Mechanical Stimulation and Scaffolds for Nucleus Pulposus Replacement of Intervertebral Disc / 대한정형외과연구학회지

PURPOSE: In this study, we investigated the potential of injectable hydrogel scaffolds for the regeneration of nucleus pulposus. MATERIALS AND METHODS: We prepared injectable hydrogels [Chitosan-Pluronic (CP), CP/Osteogenic Protein-1 (CP/OP-1), CP/Gly-Arg-Gly-Asp-Ser (CP/GRGDS), CP/GRGDS/OP-1] for this study. One of the four potential materials was selected through the cell viability tests. For each material, primary cultured nucleus pulposus (NP) cells from New Zealand rabbits were seeded onto each material. For the investigation of the effects of mechanical stimulation, the commercially available bioreactor was used. 0.2 MPa of intermittent hydrostatic pressure was imposed for 3 days after 7th day of seeding with the pattern of 2 min and 15 min for stimulating and resting, respectively. The specimens were harvested at 1, 10, 14 day after seeding for analyses. RESULTS: The MTT assay for 5 days revealed that CP/OP-1 group showed significant increase. The other two groups (CP/GRGDS and CP/GRGDS/OP-1) showed that the proliferation rate increased until 3 days after culture, while it decreased on day 5. The mechanical stimuli induced higher amounts of DNA measured in CP/OP- 1 on day 5 after culture. However, no significant difference was observed between two groups. CONCLUSION: We came to the conclusions that the biochemical environment as well as mechanical stimulation may play an important role in regenerating nucleus pulposus matrix, especially in CP/OP-1 in this study. However, further study are recommended in relation to mechanical effects as well as biochemical conditions.

A new-type non-adhesive thermosensitive liquid embolic agent for the embolization of cerebral arteriovenous malformation:an experimental study / 介入放射学杂志

Objective To synthesize a new-type thermosensitive liquid embolic material and to investigate the feasibility of using this material to occlude cerebral arteriovenous malformations (AVMs).Methods The copolymer was synthesized with N-isopropylacrylamide (NIPAM) and N-n-propylacrylamide (NNPAM),and it's physical and biological properties were estimated.The embolization of AVMs model in vitro by using this copolymer was conducted and the results were analyzed.Results The new-type copolymer possessed unique thermal behavior of lower critical soluble temperature (LCST),and it was water-soluble and non-adhesive with better biocompatibility.The successful embolization of AVMs model could be reliably obtained.Conclusion The copolymer synthesized by the authors is a new-type liquid embolic agent suitable for endovascular embolization of cerebral AVMs in vitro.Based on the results in experiment animals having been reported in medical literature,this copolymer can be further used in clinical research.