OBJECTIVETo explore the effects of S-adenosyl-L-methionine (SAM) on blood lead concentration and oxidative stress of tissue in prenatal and postnatal lead-exposed rats, and evaluate the potential reparation exerted by SAM on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in lead-exposed rat.

METHODSPregnant Wistar rats were randomly divided into three groups: control, lead-exposed and lead-exposed with SAM treatment groups. Lead-exposed rats drank 1.5 g/L lead acetate solution through pregnancy until weaning and then the pups received 20 mg/kg SAM or saline daily intraperitoneally depending on their group. Control group rats drank tap water throughout the experiment. At the postnatal 44-60 days, all the pup rats were given an extracellular recording measured in dentate gyrus (DG) area of hippocampus. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected.

RESULTSThe blood lead concentration in lead-exposed group was higher (159. 3 +/- 10. 9 microg/L) in comparing with those of control group (27.5 +/-3.8 microg/L) and lead +SAM group (33.1 +/-9.5 microg/L) (F=213.5, P<0.01). A significant recovery of liver, brain glutathione (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment (P <0.05). Chronic lead exposure during development impaired LTP measured on field excitatory postsynaptic potential (EPSP) [(112 +/-2.1)%] compared with control rats [(131+/-4.5)%] and the impaired LTP could be significantly increased by SAM treatment [(120 +/- 2.6)%] (F = 26. 1, P <0. 05).

CONCLUSIONSAM might be beneficial for treatment of lead intoxication, especially in the rescue of learning and memory impairment induced by lead and should deserve more detailed research.

Animals ; Brain ; metabolism ; Female ; Glutathione ; biosynthesis ; Lead ; blood ; Lead Poisoning ; prevention & control ; Long-Term Potentiation ; drug effects ; Male ; Maternal Exposure ; prevention & control ; Pregnancy ; Rats ; Rats, Wistar ; S-Adenosylmethionine ; pharmacology

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.
Animals ; Animals, Newborn ; Dentate Gyrus ; drug effects ; Excitatory Postsynaptic Potentials ; Fatty Acids, Omega-3 ; pharmacology ; Fish Oils ; chemistry ; Lead Poisoning ; physiopathology ; Long-Term Potentiation ; drug effects ; Perforant Pathway ; Rats ; Rats, Wistar

OBJECTIVETo explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months.

METHODSExperiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo.

RESULTSLow dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead.

CONCLUSIONMelatonin is not suitable for normal and lead-exposed children.

Animals ; Female ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Melatonin ; administration & dosage ; toxicity ; Rats ; Spatial Behavior ; drug effects

OBJECTIVETo compare the immunophenotypic and clinical characteristics between NPM1 mutated acute myeloid leukemia (AML) (NPM1m(+)AML) and unmutated AML(NPM1m(-)AML) not otherwise characterized (NOS) under similar FAB subtypes constituent ratio.

METHODSImmunophenotyping and NPM1 gene mutation type-A, B and D and other leukemic related fusion genes were detected by multiparameter flow cytometry and real time RT-PCR or PCR, respectively. 104 AML patients with NPM1m(+)AML and performed immunophenotyping assay were included, 97 with NPM1m(-)AML.

RESULTSThere were significant difference between the two groups at presentation in terms of sex, white blood count(WBC), platelet counts (PLT), blast ratio, normal karyotype ratio, WT1 expression level, FLT3-ITD mutation positive rate and remission rate of first course of induction therapy (P < 0.05). On the immunophenotype, the expression of early differentiation antigens (CD34, HLA-DR, CD117, CD38), lymphocytic antigens (CD7, CD4, CD19, CD2), myeloid and monocytic differentiation-associated antigens (CD13, CD14, CD15) were lower, and that of CD33 as well as CD123 were higher in NPM1m(+)AML patients. Among them, only CD34, HLA-DR, CD7, and CD4 positive cases were significantly lower in NPM1m(+)AML group than in NPM1m(-)AML group (P < 0.05), the rest of them had significant difference in the number of positive cells (P < 0.05). Above features were further analyzed between the M1/M2 and M4/M5 subgroups. M1/M2 cases retained the women prominent and had a higher WT1 expression level (P < 0.05). The expression of monocytic differentiation-associated antigens including HLA-DR and lymphocytic antigens were higher and that of CD117 were lower in M4/M5 subtype (P < 0.05). Among them, the positive rates of HLA-DR, CD64, CD11b, CD10, CD15, and CD4 were significantly higher in M4/M5 than in M1/M2 in NPM1m(+)AML group (P < 0.05).

CONCLUSIONThe most clinical characteristics in NPM1m(+)AML patients are consistent with reports, but some immunophenotype are different to the previous reports under similar FAB subtypes constituent ratio. The major immunophenotypic features of NPM1m(+)AML patients are lower expression of progenitor, myeloid and lymphoid lineage antigens. Monocytic differentiation-associated antigens are only higher expression in M4/M5 cases when comparison with M1/M2 cases within NPM1m(+)AML group.

Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Child ; Child, Preschool ; Female ; HLA-DR Antigens ; immunology ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Young Adult

This study was aimed to detect the expression level of cmtm 5 (CKLF-like MARVEL transmembrane domain containing member 5) gene in the bone marrow cells from patients with multiple myeloma (MM), and to investigate the correlation between the expression level of cmtm5 and various clinical characteristics. Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to measure the expression levels of cmtm5 gene in the bone marrow cells collected from MM patients, and the MM cell lines, namely, RPMI8226 and CZ1 cells. The normal donor marrow specimens were used as the reference. The ratio of cmtm5 copy number to abl (Abelson murine leukemia viral oncogene homolog) gene copy number was used for indicating the expression level. The results showed that the expression level of cmtm5 gene was significantly down-regulated in bone marrow cells of 51 untreated or relapsed/refractory MM patient as compared to those of normal donor marrow cells (0.047+/-0.062 for the untreated or relapsed/refractory MM patients versus 0.255+/-0.333 for the normal, p<0.01). According to the International Staging System (ISS), the cmtm5 expression level in marrow cells of patients in ISS III stage was significantly lower than that in patients in ISS I stage (0.034+/-0.034 for the ISS III stage versus 0.103+/-0.109 for ISSI stage, p<0.01). Similarly, lower expression levels of cmtm5 gene were also found in two human MM cell lines (0.014+/-0.009 for RPMI8226 cells and 0.004+/-0.006 for CZ1 cells). After the MM patients were effectively treated, their expression levels of cmtm5 gene significantly increased (0.020+/-0.005 for the untreated patients versus 0.227+/-0.038 for the effectively treated patients, p<0.01). A significant negative correlation was observed between the expression level of cmtm5 gene and the number of bone marrow plasma cells (r=-0.307, p<0.05). However, the correlation was not found between the expression level of cmtm5 gene and the clinical characteristics, such as gender, age, hemoglobin level, or M-protein level, etc. It is concluded that the expression level of cmtm5 gene is abnormally lower in the bone marrow cells from the MM patients, and are associated with ISS stages. Furthermore, the expression level of cmtm5 gene is negatively correlated with the number of bone marrow abnormal plasma cells in MM patients, which suggests that the abnormally lower expression of cmtm5 may be involved in the pathogenesis of the MM patients.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Staging ; Tumor Suppressor Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures.

METHODSAccording to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched.

RESULTSEach damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ).

CONCLUSIONCompression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.

Acetabulum ; injuries ; Adolescent ; Adult ; Aged ; Child ; Female ; Fractures, Bone ; classification ; diagnostic imaging ; Humans ; Male ; Medical Informatics ; methods ; Middle Aged ; Tomography, X-Ray Computed ; Young Adult

Objective: To analyze the relationship between the breast cancer molecular classification and the prognosis of patients underwent breast-conserving therapy and to discuss the safety of the breast conserving surgery from the choice of operation in terms of breast cancer molecular classification. Methods: Clinical data of 618 patients with breast-conserving therapy in Tianjin Medical University Cancer Institute and Hospital from August 2005 to August 2010 were analyzed retrospectively. According to the molecular classification when breast cancer was diagnosed, patients were subdivided into five groups, including Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative. Clinicopathological characteristics and prognosis were compared among five groups and the influencing factors of local recurrence, distant metastasis and overall survival were analyzed. Results: Among 618 patients, there were 148 cases Luminal A, 231 cases Luminal B1, 63 cases Luminal B2, 40 cases HER-2-positive and 136 cases Triple-negative. The age, family history, TNM stage, calcification, histological grade, pathological type and response to endocrine therapy of these 5 molecular types of breast cancer patients were significantly different (all P<0.05). The 5-year local regional recurrence-free survival rates of Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative were 99.3%, 98.7%, 98.4%, 94.9% and 95.9%, respectively, without significant differences (P=0.104). The 5-year distant metastasis-free survival rates of these 5 types were 97.3%, 95.7%, 93.7%, 87.5% and 91.4%, respectively, with significant differences (P=0.013). Moreover, the 5-year overall survival rates of these 5 types were 98.6%, 97.8%, 98.4%, 92.5% and 95.6%, respectively, without significant differences (P=0.153). Multifactor analysis showed that radiotherapy (HR=0.036, P=0.049) and the number of lymph node metastases (HR=10.72, P=0.004) were independent factors of local recurrence of breast cancer patients underwent breast-conserving therapy. The age (HR=0.369, P=0.046), status of surgical margin (HR=5.486, P=0.007), number of lymph node metastases (HR=2.882, P=0.023) and molecular typing (HR=5.191, P=0.008) were independent factors of distant metastasis of above breast cancer patients. None of the factors were found to be independent factors of the overall survival of these breast cancer patients. Conclusions Breast conserving therapy does not increase the risks of local recurrence and death of HER-2-positive and Triple-negative breast cancer patients. Therefore, breast conserving therapy can be accepted by patients with HER-2-positive and Triple-negative breast cancer.