Calpains, calcium-activated cysteine proteases with a neutral pH optimum, lead to degration of cystoskeletion and structural protein, and delayed neuronal death. The activation of calpains contribute to apoptosis. Calpain inhibitors provide a novel and potential treatment for cerebral ischemia due to improvement of cerebral infarct and ischemia.
Animals ; Apoptosis ; drug effects ; Brain Ischemia ; drug therapy ; metabolism ; Calcium-Binding Proteins ; therapeutic use ; Calpain ; antagonists & inhibitors ; metabolism ; physiology ; Humans

OBJECTIVETo investigate the effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with heart failure.

METHODSRabbit heart failure model was established by aortic insufficiency induced volume overload followed 14 days later by pressure overload induced by abdominal aorta constricting (HF, n = 11), another 8 rabbits with heart failure were treated with metoprolol (ME) for 6 weeks, sham-operated rabbits (n = 11) served as control. Cardiac function was measured by echocardiography at the end of study. Caffeine-induced calcium transients of myocytes loaded by Fluo-3/AM were observed under Laser scanning confocal microscope. Calcium regulatory protein expression was determined by Western blot analysis.

RESULTSCompared to control animals, the ejection fractions [EF, (45.7 +/- 3.0)% vs. (72. 6 +/- 5.0)%, P < 0.01] and the amplitude of caffeine-induced calcium transients [(16.0 +/- 3.5) FI vs. (43.5 +/- 6.2) FI, P < 0.01] were significantly decreased while its time to peak was significantly prolonged [(129.8 +/- 14.5) s vs. (52.2 +/- 7.4) s, P < 0.01] in HF rabbits. The RyR2 (0.106 +/- 0.007 vs. 0.203 +/- 0.021, P < 0.01) and the ratio of SERCA2a and NCX (1.22 +/- 0.23 vs. 1.96 +/- 0.12, P < 0.01) were also significantly reduced in myocytes of HF rabbits. Metoprolol significantly attenuated the decrease of EF [(60.2 +/- 5.1)%], the amplitude of calcium transient [(32.8 +/- 5.4) FI], the RyR2 expression (0.164 +/- 0.016) and the ratio of SERCA2a and NCX (1.68 +/- 0.17, all P < 0.05 vs. HF rabbits) and attenuated the increase of the time to peak of caffeine-induced calcium transients [(91.4 +/- 10.9) s, P < 0.05 vs. HF rabbits].

CONCLUSIONMetoprolol could improve the cardiac function possibly by preventing the alterations of calcium regulatory proteins and increasing calcium transients in failing heart.

Animals ; Aortic Valve Insufficiency ; drug therapy ; metabolism ; Calcium ; metabolism ; Calcium-Binding Proteins ; metabolism ; Disease Models, Animal ; Heart Failure ; drug therapy ; metabolism ; Metoprolol ; pharmacology ; therapeutic use ; Myocytes, Cardiac ; drug effects ; metabolism ; Rabbits

OBJECTIVEThis study examined the effect of recombinant human erythropoietin (r-HuEPO) on the serum levels of neuron-specific enolase (NSE), S-100β protein and myelin basic protein (MBP) in young rats 24 hrs after lithium-pilocarpine-induced status epilepticus (SE) in order to study the potential role of r-HuEPO in epileptic brain damage.

METHODSForty 19-21-day-old male Sprague-Dawley (SD) rats were randomly divided into four groups (n=10): normal control group, SE, r-HuEPO pretreated-SE and r-HuEPO. SE was induced by lithium-pilocarpine. R-HuEPO (500 IU/kg) was intraperitoneally injected in the r-HuEPO pretreated-SE and r-HuEPO groups 4 hrs before SE. Serum levels of NSE, S-100β and MBP were determined 24 hrs after the SE event.

RESULTSSerum levels of NSE, S-100β and MBP in the SE group increased significantly compared with those in the normal control and the r-HuEPO groups (P＜0.05). The r-HuEPO pretreated-SE group showed significantly decreased serum levels of NSE, S-100β and MBP compared with the SE group (P＜0.05).

CONCLUSIONSr-HuEPO may reduce the expression of NSE, S-100β and MBP and thus might provide an early protective effect against epileptic brain injury.

Animals ; Erythropoietin ; pharmacology ; therapeutic use ; Male ; Myelin Basic Protein ; blood ; Nerve Growth Factors ; blood ; Phosphopyruvate Hydratase ; blood ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood ; Status Epilepticus ; blood ; drug therapy

OBJECTIVETo evaluate the effect of ulinastatin on post-operative Cognition disorders in elderly patients undergoing hip joint replacement.

METHODSForty ASA I or II elderly patients undergoing selective hip joint replacement, aged > or = 65 years, were randomly divided into 2 groups (n = 40 each): control group and ulinastatin group. Ulinastatin group received iv infusion of ulinastatin (10,000 u/kg) after skin incision, (5,000 U/kg) after operation 1, 2, 3 d respectively, included 21 males and 19 females with an average age of (75.00 +/- 7.81) years old. Control group received the same volume of normal saline instead of ulinastatin, included 20 males and 20 females with an average age of (72.80 +/- 7.25) years old. Neuroeognitive testing was performed on the preoperative day and on the 3th postoperative day and post-operative cognition disorders was defined as 1 SD decline from baseline on neurocognitive assessment. Serum S100beta protein were measured before operation, at the end of surgery, 3, 24 h and 3 d after operation.

RESULTSThe incidence rate of postoperative cognition disorders was 2.5% in ulinastatin group, there were lower than those of patients in the control group (25%) (P < 0.05); In control group, the scales for MMSE before and after operation were (25.2 +/- 2.1), (22.6 +/-2.5) scores and the level of serum S100beta protein at T0-4 were (0.041 +/- 0.012), (0.125 +/- 0.031), (0.178 +/- 0.036), (0.142 +/- 0.038), (0.048 +/- 0.015) microg/L. As well in ulinastatin group, above date were (25.9 +/- 2.4), (24.8 +/- 2.1), (0.040 +/- 0.013), (0.095 +/- 0.021), (0.116 +/- 0.017), (0.087 +/- 0.019) and (0.043 +/- 0.012) respectively. Compared with preoperative, MMSE evaluation scale was decreased on the 3th postoperative day and the S100beta was increased markedly at T1-3 in control group (P < 0.05); Compared with control group, MMSE evaluation scale was increased and the S100beta was decreased markedly at T1-3 in ulinastatin group (P < 0.05 ).

CONCLUSIONIntravenous infusion of ulinastatin during operation can prevent the occurrence of POCD in elderly patients.

Aged ; Arthroplasty, Replacement, Hip ; adverse effects ; Cognition Disorders ; blood ; drug therapy ; Female ; Glycoproteins ; therapeutic use ; Humans ; Male ; Nerve Growth Factors ; blood ; Postoperative Complications ; blood ; drug therapy ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female ; Animals ; Humans ; Mice ; Candidiasis, Vulvovaginal/drug therapy* ; Inflammasomes/genetics* ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; 1-Butanol/pharmacology* ; Fluconazole/therapeutic use* ; Interleukin 1 Receptor Antagonist Protein/therapeutic use* ; Mice, Inbred C57BL ; Candida albicans ; Cytokines ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; RNA, Messenger ; Calcium-Binding Proteins/therapeutic use*

Actins ; metabolism ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Calcium-Binding Proteins ; metabolism ; Carcinoma ; metabolism ; pathology ; Cyclophosphamide ; therapeutic use ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Fibrosarcoma ; metabolism ; pathology ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Humans ; Leiomyosarcoma ; drug therapy ; metabolism ; pathology ; surgery ; Mastectomy, Segmental ; Methotrexate ; therapeutic use ; Microfilament Proteins ; metabolism ; Neurilemmoma ; metabolism ; pathology ; Phyllodes Tumor ; metabolism ; pathology ; Postoperative Period ; Vimentin ; metabolism

OBJECTIVE: To investigate the protective effect of aminophylline on cerebral injury induced by cardiopulmonary bypass (CPB) in infants. METHODS: Forty patients who underwent ventricular septal defect within 3 years old were randomly divided into 2 groups(20 cases in each group).Aminophylline group:aminophylline (5 mg/kg) was injected slowly via the vein after anesthesia and maintained at a dose of 0.5 mg/(kg.h) until the end of CPB. CONTROL GROUP: aminophylline was replaced by Ringer's lactated solution. Samples were obtained at the beginning of CPB (T(1)),the end of CPB (T(2)),6 h (T(3)) and 24 h (T(4)) after the operation to measure S-100 beta protein, NSE, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and interleukin-10 (IL-10) concentration by ELISA in the 2 groups. RESULTS: Compared with the time point immediately before CPB, the S-100beta protein,NSE, TNF-alpha, and IL-8 concentration in the 2 groups began to increase with the start of CPB, reached a climax at the end of CPB (T(2)),decreased gradually 6 h after the termination of CPB(T(3)) and could not restore to the level before CPB at T(4)(24 h after the termination of CPB).IL-10 in the 2 groups both increased after the CPB. At T(2) and T(3), S-100beta protein,NSE, TNF-alpha, and IL-8 concentrations were significantly lower than those in the aminophylline group (P<0.05 or P<0.01), while IL-10 was just the opposite. CONCLUSION There is cerebral damage induced by CPB. Aminophylline may play a protective role in cerebral injury by modulating the balance between the pro-inflammatory factor and anti-inflammatory factor to reduce the level of S-100beta protein and NSE during CPB and open cardiac surgeries.
Aminophylline ; administration & dosage ; therapeutic use ; Brain Diseases ; etiology ; prevention & control ; Cardiopulmonary Bypass ; adverse effects ; Cardiovascular Surgical Procedures ; Child, Preschool ; Female ; Heart Septal Defects ; drug therapy ; surgery ; Humans ; Infant ; Injections, Intravenous ; Male ; Nerve Growth Factors ; blood ; Neuroprotective Agents ; therapeutic use ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood

OBJECTIVETo investigate the effects of preconditioning and postconditioning with Shenfu Injection (SFI) on cognitive function in patients after valve replacement under extra-corporeal circulation.

METHODSThirty-two patients prepared to receive valve replacement, aged 25-54 years, with heart function of II-III level, were randomly assigned to four groups, eight in each group. Patients in group E1 received SFI 1 mL/kg after intubation and before blocking the aorta; patients in group E2 received SFI 1 mL/kg after opening the aorta; patients in group E3 received SFI 0.5 mL/kg twice, at before blocking and after opening the aorta, respectively; and patients in group C received 1 mL/kg normal saline after intubation for control. All the medication was infused via pump. Venous blood samples were taken from the internal jugular venous bulb cannula for detecting plasma S100beta protein by ELISA at 6 different time points, i.e. after trachea intubation (T1), 10 min after cardiopulmonary bypass (CPB, T2), hypothermia stabilizing stage (T3), re-warming to 33 degrees C (T4), ending CPB (T5) and 1 h after ending CPB (T6). And patients' cognitive function was assessed for 4 times with mini-mental state examination (MMSE) scale, at the day before operation, and 1, 2, 7 days after operation.

RESULTSThe elevation of S100beta plasma protein was lesser in the three E groups than that in group C (P < 0.05), and the lowest level was shown at T6 in Group E3 (P < 0.05). The highest incidence of cognitive dysfunction occurred in Group C one week after operation (P < 0.05).

CONCLUSIONSFI may reduce the plasma level of S100B protein, maintain stable the structure and function of blood-brain barrier, it is favorable to the post-operational recovery of neurological function of patients, showing good brain protective effect. The optimal effect could be obtained by pump infusion of 0.5 mL/kg of SFI before aortic blocking and after aortic opening.

Adult ; Blood-Brain Barrier ; drug effects ; Brain ; blood supply ; Cardiopulmonary Bypass ; Cognition Disorders ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Valve Prosthesis Implantation ; Humans ; Ischemic Preconditioning ; Male ; Middle Aged ; Nerve Growth Factors ; blood ; Phytotherapy ; Postoperative Complications ; prevention & control ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood