The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.
Antifungal Agents ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Drug Synergism ; Fungi ; drug effects

Objective To determine the effects of urapidil on L-type calcium current(I_(Ca-L))in rat cardiomyocytes.Methods Ventricular myocytes were isolated from SD rats of either sex(250-280g)by retrograde perfusion of the hearts via aorta with calcium-free Tyrode solution containing enzyme as described elsewhere.Rod shaped cells with clear borders and striations were selected.Eighteen cells were randomly divided into 3 groups(n =6 each):A urapidil group;B urapidil+methysergide group and C methysergide group.All the cells in the three groups were peffused first with Tyrode solution for 1 min(T_1).In group A and C cells were then peffused with Tyrode solution containing 0.4 ?mol?L~(-1) urapidil(A)or 40 nmol?L~(-1) methysergide(C)for 1 min(T_2) while in group B cells were perfused fwst with Tyrode solution containing 0.4 ?mol?L~(-1) urapidil for 1 min (T_2) then with Tyrode solution containing methysergide 40 nmol?L~(-1) for 1 min (T_3).Finally the cells were again perfused with regular Tyrode solution for 1 min(T_4)to wash out the drugs.The peak of I_(Ca-L) was recorded at T_(1-4) by means of the whole cell patch clamp technique with use of Axo patch 200B.Results In group A,B and C the peak of I_(ca-L) at T_2 was significantly lower than that at T_1 but there was no significant difference between the peak of I_(ca-L) at T_1 and T_4.In group B the peak of I_(Ca-L) at T_3 was significantly lower than that at T_2.Conclusion Urapidil inhibits L-type calcium current in rat isolated cardiomyoeytes.It's inhibitory effect may not be mediated by 5-H_(1A) receptor.

Objective:To investigate the variations in ocular biometry and its influencing factors in adult Tibetans of Lhasa.Methods:A cross-sectional study was adopted.A total of 100 consecutive adult Tibetans (100 eyes) with cataract, who were treated in Tibet Autonomous Region People's Hospital from March 2017 to July 2017 were enrolled, including 51 males and 49 females, with an average age of (63.38±12.80) years.The subjects were divided into two groups, with 57 subjects (57 eyes) older than 60 years in the elder group and 43 subjects (43 eyes) younger than 60 years in the youth group.Corneal curvature, corneal astigmatism, anterior chamber depth and axial length of subjects were measured and compared with those of Beijing population which were used as standardized data of Han Chinese.The differences in ocular parameters associated with age and gender were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Tibet Autonomous Region People's Hospital (No.ME-TBHP-21-KJ-005).Written informed consent was obtained from each subject prior to any examination.Results:The mean corneal curvature, corneal astigmatism, anterior chamber depth and axial length of the 100 Tibetans were (43.68±1.62)D, 0.750 (0.375, 1.000)D, (3.05±0.41)mm, (23.07±0.86)mm, respectively.The axial length of Tibetan was shorter than that of Beijing Han people and the difference was significant ( t=2.65, P<0.01).Corneal astigmatism of the elder group was higher than that of youth group and the difference was significant ( t=2.11, P<0.05).There were no significant differences in corneal curvature, anterior chamber depth and axial length between the elder group and youth group (all at P>0.05).The anterior chamber depth and axial length of males were much longer than those of females, and the differences were significant ( t=2.71, 2.25; both at P<0.05). Conclusions:In adult Tibetan population, the axial length is short, and the anterior chamber is deep.The corneal astigmatism increases with age and there is a gender difference in axial length and anterior chamber depth.

Adolescent ; Anticoagulants ; therapeutic use ; Body Temperature ; Child ; Child, Preschool ; Critical Illness ; therapy ; Female ; Hemodynamics ; Hemofiltration ; Humans ; Infant ; Male

OBJECTIVESTo analyze the reliability and clinical value of intraoperative ultrasound combined with neuronavigation for resection of intracranial cavernous malformations.

METHODSFrom January 2007 to December 2009, 40 cases of intracranial cavernous malformations were operated under the application of intraoperative ultrasound combined with neuronavigation. There were 18 male and 22 female, aged 18 to 58 years, with a mean age of 34.5 years. Neuronavigation was used for all patients before operation to display the three-dimensional model of nervous system and lesions, so to design the operative approach and determine the scope of the incision. Lesions were allocated by real-time neuronavigation in order to continuously verify the accuracy of operative approach during the operation, supplemented by real-time monitoring of intraoperative ultrasound to guide the process of surgery and determine the extent of resection of lesions.

RESULTSThe registration error of neuronavigation was 1.3 - 3.2 mm, with an average of 2.0 mm. All the patients' three-dimensional model of nervous system and lesions were satisfactorily displayed, and the area of lesions were all accurately located. Structural brain-shifts occurred in 4 cases in the remove process of the lesion, with shift degree 5.0 - 10.0 mm, and were corrected by intraoperative ultrasound. All lesions were well displayed by intraoperative ultrasound. Gross total resection was achieved in all patients, with no patient infected or dead. Neurological deterioration was seen in 2 patients, the morbidity was 5.0%.

CONCLUSIONSThe combination of neuronavigation and intraoperative ultrasound for resection of intracranial cavernous malformations can provide valuable intraoperative informations of the location and resection level of the lesion, thereby maximize the accuracy of lesion localization and the extent of resection, with less complications and enhanced efficacy of the surgery.

Adolescent ; Adult ; Female ; Hemangioma, Cavernous, Central Nervous System ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Neuronavigation ; Neurosurgery ; methods ; Ultrasonography ; Young Adult

OBJECTIVETo evaluate the utility of neuronavigation in the microsurgery for cerebral cavernous malformations.

METHODSIn a retrospective study, 47 patients with cavernous malformations were involved from January 1995 to December 2010. Fourteen cases admitted into hospital from January 1995 to December 2002 were treated without neuronavigation (conventional group), the focus localization was based on magnetic resonance imaging (MRI) images, anatomic landmarks, and the experiences of the neurosurgeon. In the other 33 cases admitted after February 2002 to December 2010, surgeries were performed with neuronavigation using the Medtronic Stealth Station TREON or TRIA system (neuronavigation group). Excision of the cavernomas were all performed microsurgically, surrounding gliotic rim and hemosiderin stained tissue were resected in the case of epilepsy, and a few patients underwent extended hippocampal resection or multiple subpial transection.

RESULTSWith the use of neuronavigation, the extent of craniotomy reduced from 5.2 cm to 3.6 cm (P < 0.01), and deeper cavernoma focuses could be treated surgically. There were no changes with regard to the mean size of the cavernomas, the mean time of surgery and hospital stay (P > 0.05), but the mean time of anaesthesia was prolonged from 164 min to 197 min (P < 0.01). Cavernomas were resected completely in all 47 cases, which was confirmed by postoperative MRI recheck. The conditions of all patients were improved or remain unchanged, and no significant differences in the clinical outcome could be evaluated between the two groups.

CONCLUSIONSApplication of neuronavigation-assisted microsurgery of intracranial cavernous malformations surgery, helps reduce the surgical trauma, and has security and reliability.

Adolescent ; Adult ; Female ; Hemangioma, Cavernous, Central Nervous System ; surgery ; Humans ; Male ; Microsurgery ; methods ; Middle Aged ; Neuronavigation ; Retrospective Studies ; Young Adult

OBJECTIVETo study the chemical constituents of the root of Paeonia sinjiangensis.

METHODThe constituents were isolated by silica column chromatography, and their structures were identified on the basis of spectral analysis and their physical-chemical constants.

RESULTFive compounds, paeoniflorin( I ), albiflorin (II), lactiflorin(III), daucosterol(IV), sucrose (V), were obtained.

CONCLUSIONAll of the compounds were obtained from this plant for the first time.

Benzoates ; chemistry ; isolation & purification ; Bridged-Ring Compounds ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Glycosides ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Monoterpenes ; chemistry ; isolation & purification ; Paeonia ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo evaluate the practicability and validity of transcranial magnetic motor evoked potential monitoring (TMS-MEP) during spinal surgery.

METHODSFrom February 2001 to June 2004, 37 patients undergoing spinal surgery were involved, anaesthesia was maintained with volatile anesthetics in 11 operations and etomidate in 26. Analgesia was provided with fentanyl, and non-depolarizing muscle relaxant was given intermittently. MEPs elicited with transcranial magnetic stimulations were recorded from tibialis anterior muscles, simultaneously bispectral index (BIS) and train-of-four stimulation (TOF) were used to monitor the anesthesia depth and neuromuscular blockade respectively. The variety of MEP and its effect on surgical operation at different anesthesia depth and muscular relaxation were observed, and the muscle strength of the patients before and after operation were compared.

RESULTSThe 11 cases anesthetized with isoflurane or enflurane gave no response to TMS, the other 26 cases in which anaesthesia was maintained with etomidate and fentanyl gave satisfactory TMS-MEPs, but with significantly attenuated amplitudes and prolonged latencies (P < 0.05). Intraoperative MEP showed a grossly unchanged waveform, and its amplitude and latency had little fluctuation when anaesthesia and neuromuscular blockade maintained stable. When T(1) value of TOF at 40% - 60%, a steady MEP could be acquired and the muscular contraction after TMS should not interfere the operation.Seven of 26 cases had a MEP amplitude drop up to 50% or more during the operation, the surgical team was notified to avoid further spinal injury, at last only 1 case had a worsen muscle power after operation.

CONCLUSIONSMyogenic TMS-MEP is a valid and practicable technique for intraoperative monitoring, and the etomidate + fentanyl technique is adequate for its anesthesia. BIS and TOF monitoring are helpful to maintain the steadiness of the anesthesia and MEPs, which is very important for monitoring the changes of the MEPs.

Adolescent ; Adult ; Aged ; Anesthesia ; methods ; Evoked Potentials, Motor ; physiology ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Spinal Cord ; surgery ; Spine ; surgery ; Transcranial Magnetic Stimulation ; Young Adult

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Polyamides, containing N-methylpyrrole (Py) and N-methyl-imidazole (Im) amino acids, are synthetic oligomers programmed to read the DNA double helix in the minor groove with high affinities and sequence specificities resulting in modulation of gene expression. They are cell permeable, stable and have no cytotoxicity, which provide a promising tool of gene regulation. We describe here recent advances in the field of DNA binding polyamides, including pairing rules, specifities and affinities to DNA, synthesis methods, cellular and nuclear uptake properties, gene regulation and effectiveness in vivo. The potential problems and difficulties in future research are also discussed.
Animals ; Base Pairing ; DNA ; chemistry ; genetics ; DNA Footprinting ; Gene Expression Regulation ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; metabolism ; pharmacology ; Nylons ; chemical synthesis ; chemistry ; metabolism ; pharmacology ; Pyrroles ; chemical synthesis ; chemistry ; metabolism ; pharmacology