ABSTRACT
Disease can act as a driving force in shaping genetic makeup across populations, even species, if the impacts influence a particularly sensitive part of their life cycles. White-nose disease is caused by a fungal pathogen infecting bats during hibernation. The mycosis has caused massive population declines of susceptible species in North America, particularly in the genus Myotis. However, Myotis bats appear to tolerate infection in Eurasia, where the fungal pathogen has co-evolved with its bat hosts for an extended period of time. Therefore, with susceptible and tolerant populations, the fungal disease provides a unique opportunity to tease apart factors contributing to tolerance at a genomic level to and gain an understanding of the evolution of non-harmful in host-parasite interactions. To investigate if the fungal disease has caused adaptation on a genomic level in Eurasian bat species, we adopted both whole-genome sequencing approaches and a literature search to compile a set of 300 genes from which to investigate signals of positive selection in genomes of 11 Eurasian bats at the codon-level. Our results indicate significant positive selection in 38 genes, many of which have a marked role in responses to infection. Our findings suggest that white-nose syndrome may have applied a significant selective pressure on Eurasian Myotis-bats in the past, which can contribute their survival in co-existence with the pathogen. Our findings provide an insight on the selective pressure pathogens afflict on their hosts using methodology that can be adapted to other host-pathogen study systems.
Subject(s)
Chiroptera , Selection, Genetic , Chiroptera/microbiology , Chiroptera/genetics , Animals , Host-Pathogen Interactions/genetics , Genome , Mycoses/microbiology , Mycoses/veterinary , Evolution, Molecular , Genomics/methods , Whole Genome SequencingABSTRACT
OBJECTIVE: To investigate the effects of early rehabilitation training after total knee arthroplasty surgery by continuous femoral nerve block (CFNB) with or without periarticular local infiltration analgesia (PLIA). METHODS: In this randomized, double-blind, controlled study, 100 patients under-going primary unilateral total knee arthroplasty in patients with knee osteoarthritis were enrolled. All the patients received CFNB for postoperative analgesia before combined spinal epidural anesthesia. They were randomly divided into 2 groups (n=50 each): CFNB group, CFNB combined with PLIA group (PLIA group). Group PLIA received periarticular local infiltration analgesia with 20 mL ropivacaine (5 g/L), while the equal volume of normal saline was used instead of ropivacaine in group CFNB. Postoperative pain during rest and passive exercises including front and rear portions of knees, the time of ability to perform an active straight leg raise, the time of ability to reach 90° knee flexion, and preoperative and postoperative hospital for special surgery knee score (HSS) were evaluated. RESULTS: Compared with group CFNB, the visual analogue scores (VAS) of front of knees at rest time in group PLIA had no significant difference (P>0.05); there were significant differences at 4, 8, 12, 24 h postoperation in portions of knees at rest time (P<0.05); the VAS had significant differences at 24 h in passive exercises of knees (P<0.05); the VAS had significant differences at 12, 24 h in portions of knees at passive exercises of the knees (P<0.05); the time of ability to perform an active straight leg raise had significant differences in the two groups (P<0.05). CONCLUSION: Compared with CFNB postoperative analgesia alone, CFNB with PLIA could relieve rest pain and pain during passive movement after total knee arthroplasty. CFNB with PLIA could shorten the time to perform an active straight leg raise and the time of ability to reach 90° knee flexion. And so some patients could improve postoperative rehabilitation training.
Subject(s)
Amides/administration & dosage , Amides/therapeutic use , Analgesia/methods , Arthroplasty, Replacement, Knee/rehabilitation , Nerve Block/methods , Recovery of Function/drug effects , Anesthesia, Local/methods , Double-Blind Method , Femoral Nerve/drug effects , Humans , Pain Management , Pain, Postoperative/drug therapy , Postoperative Period , Range of Motion, Articular/drug effects , Ropivacaine , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the effect of active fraction A in Guizhi Decoction (Fr.A) on dual-directional thermoregulation and its mechanism of influencing heat shock protein (HSP) in hypothalamus. METHOD: Using Western blot method to measure HSP of hypothalamus in febrile and hypothermal rats. RESULTS: Regulating the body temperature in dual-direction, Fr.A could antagonize the decrease of HSP contents of hypothalamus in hypothermal rats induced by aminopyrine, and abate the HSP content in febrile rats induced by yeast. CONCLUSION: Fr.A adjusts the body temperature through regulating the contents of HSP of hypothalamus in febrile and hypothermal rats.
Subject(s)
Body Temperature Regulation/drug effects , Drugs, Chinese Herbal/pharmacology , Fever/metabolism , Heat-Shock Proteins/metabolism , Hypothermia/metabolism , Animals , Drug Combinations , Fever/chemically induced , Hypothalamus/metabolism , Hypothermia/chemically induced , Male , Random Allocation , Rats , Rats, WistarABSTRACT
Liuwei Dihuang Decoction is a representative classic prescription for nourishing Yin in Traditional Chinese Medicine. Experimental and clinical studies showed that the recipe could 1. inhibit carcinogenesis of anterior stomach by N-nitrososarcosine ethyl ester in mice; 2. inhibit the formation of lung tumors induced by Urethan in mice; 3. decrease spontaneous tumorigenesis in LACA strain; 4. inhibit the mutagenic activity of Endoxan in micronuclear test. Patients with epithelial dysplasia of esophagus, a preneoplastic lesion, were treated by using this recipe. The canceration rate within 1 year was 2.2% in the treated and 12.4% in an untreated group. Within 5 years these rates were 9% and 26% respectively (p less than 0.025).
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Esophageal Neoplasms/prevention & control , Animals , Cell Nucleus/drug effects , Cell Nucleus/pathology , Cyclic AMP/biosynthesis , Cyclophosphamide/antagonists & inhibitors , Cyclophosphamide/toxicity , Drugs, Chinese Herbal/pharmacology , Epithelium/drug effects , Epithelium/pathology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Female , Humans , Hyperplasia , Lung Neoplasms/chemically induced , Lung Neoplasms/prevention & control , Mice , Mutagenicity Tests , Mutation , Neoplasms, Experimental/chemically induced , Neoplasms, Experimental/immunology , Neoplasms, Experimental/pathology , Nitrosamines , Phagocytosis/drug effects , Precancerous Conditions/drug therapy , Precancerous Conditions/pathology , Spleen/drug effects , Spleen/pathology , Stomach Neoplasms/chemically induced , Stomach Neoplasms/prevention & control , Thyroid Gland/drug effects , Thyroid Gland/physiopathology , Urethane , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/mortalitySubject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Medicine, East Asian Traditional , Neoplasms, Experimental/drug therapy , Plant Extracts/therapeutic use , Animals , Cyclic AMP/analysis , Esophageal Neoplasms/drug therapy , Humans , Immunity/drug effects , Mice , Nucleic Acids/analysis , Precancerous Conditions/drug therapy , Thyroid Gland/drug effectsABSTRACT
The antitumor activity of four investigational natural products (camptothecin, harringtonin, cantharidin and curcumae) obtained from China were tested on human tumor biopsies in an in vitro soft agar clonogenic assay system. Significant antitumor activity was seen with camptothecin against human ovarian cancer and some other adenocarcinomas. Antitumor activity was also observed for harringtonin against adenocarcinoma and sarcoma. Both drugs also appeared to show activity in melanoma and mesothelioma. However, cantharidin and curcumae were relatively ineffective on the human tumors tested. For purposes of comparing the intensity of antitumor effects with standard cytotoxic drugs to those of the four new agents, the ID50 values were calculated. The ratio of ID50S of new drugs to the standard agents doxorubicin, cis-platinum and vinblastine (ID50 of the standard drug/ID50 of tested drug) were 10.2, 64.1 and 1.9 for camptothecin and 1.5, 10.3 and 0.9 for harrington respectively. A relationship was observed between the duration of drug exposure (1 hr prior to plating vs continuous contact in the agar) and inhibition of clonogenic tumor cells for camptothecin, harringtonin and doxorubicin.
Subject(s)
Alkaloids/pharmacology , Camptothecin/pharmacology , Cantharidin/pharmacology , Catechols/pharmacology , Curcumin/pharmacology , Harringtonines/pharmacology , Neoplasms/pathology , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Colony-Forming Units Assay , Dose-Response Relationship, Drug , HumansABSTRACT
In vitro studies of the schedule dependency and cytotoxicity of didemnin B, a novel depsipeptide isolated from a Carribean tunicate (Didemnidae), were carried out in fresh tumor cells obtained from biopsies from 39 cancer patients using the human tumor stem cell assay. Two schedules of drug exposure were examined (1 h and continuous exposure in the agar). Tumor cells from nine of 26 patients (34.6%) showed reduced survival of tumor-colony forming units to 30% of control or less at the 0.01 microgram level in the continuous exposure studies. Cells from eight of 17 patients (47%) showed a similar degree of sensitivity to didemnin after a 1-h exposure to 0.1 microgram prior to plating. The median ID50 values were 4.2 X 10(-3) micrograms/ml and 46 X 10(-3) micrograms/ml for continuous and 1-h exposures, respectively. A clear dose-response relationship was observed with both dosage schedules. Comparison of the slopes of the continuous and 1-h exposures and of the ID50 of the drug schedules suggests that didemnin is a cell-cycle-non-specific cytotoxic agent. Significant in vitro antitumor activity was observed at low concentrations against carcinomas of the breast, ovary, and kidney, and also mesothelioma and sarcoma. These results can provide pharmacologic goals to be achieved in phase I clinical trial. Further in vitro testing should help select tumor types for study in phase II trials of this very promising new anticancer drug.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Depsipeptides , Hematopoietic Stem Cells/drug effects , Neoplasms/pathology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Humans , In Vitro Techniques , Peptides, Cyclic/pharmacology , Time FactorsABSTRACT
Harringtonine and its derivative homoharringtonine are ester-containing anti-leukemic alkaloids isolated from the tree Cephalotaxus harringtonia. In order to compare their antitumor activity against solid tumors, in vitro culture of fresh tumor cells from 23 patients was carried out with a soft agar assay system. Tumor cells were exposed to 0.001-1.0 micrograms/ml of each agent for either 1 h prior to plating or by continuous exposure. Significant antitumor activity was noted for harringtonine in ovarian and endometrial carcinoma at the 0.01 micrograms/ml concentration. In the continuous exposure studies, homoharringtonine proved to be more potent than harringtonine. Significant antitumor activity of homoharringtonine was noted in sarcoma and breast cancer as well as in ovarian and endometrial carcinoma. In the continuous exposure studies the mean area under the survival-concentration curve was significantly less for homoharringtonine than for harringtonine (5.04 +/- 3.87 and 6.15 +/- 3.46, respectively (p less than 0.005). The ratio of mean ID50 (harringtonine/homoharringtonine) was 5.2. However, there was no significant difference between those two agents with a 1 h exposure. Our results suggest that homoharringtonine and harringtonine may be of use in selected solid tumors, and that homoharringtonine has a greater degree of colony inhibition with continuous exposure.