Modulators of growth in primary culture of rat proximal tubular cells II

Summary: The present studies assessed the effects of manipulating extracellular sodium (Na) concentration and Na transport on cellular hypertrophy and hyperplasia in primary culture of rat proximal tubular cells. A concentration-dependent effect on thymidine incorporation and protein content was observed with cell culture media Na concentration of 130, 140 and 150 mmol/L. This effect was independent of osmolality (matched with mannitol) and no stimulatory effect occurred if choline was substituted for Na. Cells derived from sham-operated (Sx) animals exposed to a higher media concentration of Na (150 vs 140 mmol/L) had both stimulated thymidine incorporation to 186.8 ± 35.41% (P<0.05) and enhanced cell protein content to 134.7 ± 135% (P<0.05). This effect was more pronounced in cell cultures derived from unilaterally nephrectomized (Nx) animals, being 212.8 ± 31.5% (P<0.01) for thymidine incorporation (P<0.05 vs cells from sham-operated animals grown in high Na media) and 114.4 ± 3.2% (P<0.001) for protein content (P=0.11 vs sham-operated cells grown in similar conditions). the addition of 10^?4 mmol/L ethylisopropyl amiloride hydrochloride (EIPA) to Nx cells in a normal or high Na concentration media resulted in a decrease in cellular protein content to 82.6 ± 6.8% (P<0.05) and 85.5 ± 0.2% (P<0.0001) compared to respective controls. 10^?4 mol/L EIPA in media supplemented with insulin-like growth factor (IGF-1) blocked the proliferative response normally seen in response to this growth factor from 156.6 ± 13.7 to 27.5 ± 3.1% (P<0.0001) compared to control. However, the presence of EIPA did not abrogate the hypertrophic response elicited by IGF-1 (cell protein content 128.1 ± 13.1% of control with IGF-1 vs 124.9 ± 12.5 with IGF-1 and EIPA; P= n.s.). Addition of 10^?4 mol/L EIPA to 10% serum derived from either Sx or Nx animals blocked the growth response to the sera, limiting the cellular protein content to 76.6 ± 5.5% (P<0.0001) and 89.7 ± 4.4% (P<0.0001) and thymidine incorporation to quiescent levels of 0.2 ± 0.1% (P<0.0001) and 0.4 ± 0.1% (P<0.0001) compared to respective controls. In summary, rat renal proximal tubular cell growth is influenced by Na concentrations in the cell culture environment and inhibited in the presence of EIPA. This supports a role for altered epithelial transport in the cellular growth response to a number of stimuli.     

论医学生和谐就业伦理观的培养

结合目前医学生在就业过程中出现的不和谐伦理现象,分析了其主客观原因,提出了医学生和谐就业伦理观培养的现实途径.     

Immunohistochemical study of lymph nodes in patients with cat scratch disease.

BACKGROUND/PURPOSE: Bartonella henselaeis the causative agent of cat scratch disease (CSD), manifesting as fever and acute regional lymphadenopathy. Although serologic testing is the reference method for diagnosis, successful use of immunohistochemical (IHC) stain of regional lymph nodes for the diagnosis of CSD has been reported. To determine the characterization and diagnostic potential of IHC in lymphadenopathy of CSD, lymph nodes were excised from patients with suspected CSD for further evaluation. METHODS: Polyclonal antibody-based IHC studies were performed for the detection of B. henselae. Between January 2001 and December 2004, the reference laboratory of the Center for Disease Control, Taiwan, received a total of 377 sera from 352 reported suspected CSD cases. Twenty-three formalin-fixed paraffin-embedded lymph nodes from 16 patients and two skin biopsies from two patients suspected of having CSD were included in this study. Nine of them were serologically confirmed to have CSD and the others were seronegative but suspected to have CSD by the attending physicians. Seven lymph node specimens were obtained from tuberculosis patients for comparison. RESULTS: We demonstrated that the microorganisms existed in the cytoplasm of histiocytes within the granulomatous lesions in nine lymph nodes and one skin biopsy. Among the nine lymph nodes with IHC (+) stains, three were seronegative. On the other hand, three cases were IHC (+) and six cases were IHC (-) among nine seronegative patients. In addition, two seronegative patients with skin biopsy showed one IHC (+) and one IHC (-). CONCLUSION: IHC can contribute to the etiologic diagnosis of B. henselaelymphadenopathy when serology and molecular techniques are not available.     

Obesity in Diabetic Patients Undergoing Coronary Artery Bypass Graft Surgery Is Associated with Increased Postoperative Morbidity

Background: Despite the fact that obesity is a known risk factor for cardiovascular disease, many studies have failed to demonstrate that obesity is independently associated with an increased risk of cardiovascular morbidity and mortality in nondiabetic patients undergoing coronary artery bypass graft surgery. The authors investigated the influence of obesity on adverse postoperative outcomes in diabetic and nondiabetic patients after primary coronary artery bypass surgery.

Methods: A retrospective cohort study of patients undergoing primary coronary artery bypass surgery (n = 9,862) between January 1995 and December 2004 at the Texas Heart Institute was performed. Diabetic (n = 3,374) and nondiabetic patients (n = 6,488) were classified into five groups, according to their body mass index: normal weight (n = 2,148), overweight (n = 4,257), mild obesity (n = 2,298), moderate obesity (n = 785), or morbid obesity (n = 338). Multivariate, stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications to determine whether obesity was independently associated with an increased risk of adverse postoperative outcomes.

Results: Obesity in nondiabetic patients was not independently associated with an increased risk of adverse postoperative outcomes. In contrast, obesity in diabetic patients was independently associated with a significantly increased risk of postoperative respiratory failure (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.41-3.61; P < 0.001), ventricular tachycardia (OR, 2.27; 95% CI, 1.18-4.35; P < 0.02), atrial fibrillation (OR, 1.56; 95% CI, 1.03-2.38; P < 0.04), atrial flutter (OR, 2.38; 95% CI, 1.29-4.40; P < 0.01), renal insufficiency (OR, 1.66; 95% CI, 1.10-3.41; P < 0.03), and leg wound infection (OR, 5.34; 95% CI, 2.27-12.54; P < 0.001). Obesity in diabetic patients was not independently associated with an increased risk of mortality, stroke, myocardial infarction, sepsis, or sternal wound infection.     

浆膜受侵的结直肠癌术后腹腔化疗联合静脉化疗的临床研究

Objective To compare the clinical efficacy of postoperative intraperitoneal chemotherapy combined with systemic chemotherapy to systemic chemotherapy alone for serosa-involved colorectal cancer. Methods According to the criteria of serosa-involving in colorectal cancer, 332 cases were divided into 2 groups prospectively without randomization. Study group (n=166) was treated with intraperitoneal chemotherapy combined with systemic chemotherapy, and control group (n=166) with systemic chemotherapy alone. Incidence of local recurrence, peritoneal metastasis, hepatic metastasis, other distant metastasis and 3-year, 5-year overall survival (OS) rate of two groups were compared. Results 3-year and 5-year OS rates of stage Ⅱ B in study group were similar to those in control group (χ2=0.612,P=0.434). The above rates of stage Ⅲ in study group were higher than those in control group (χ2=3.989,P=0.046). Either the study group or the control group, the 3-year and 5-year OS rates of patients undergone laparoscopic surgery or open surgery were similar (P=0.839, P=0.172). Incidences of local recurrence, peritoneal metastasis and hepatic metastasis in study group were 1.9%, 3.8% and 3.8% respetively, lower than those in control group (8.2%,9.5% and 10.1%,P<0.05). Distant metastasis rate in study group was similar to that in control group. In study group, intraperitoneal chemotherapy regimen with Oxaliplatin had lower rates of peritoneal metastasis and hepatic metastasis as compared to that with Cisplatin (0.9% vs 8.8% ,P=0.019), while the incidences of local recurrence and other distant metastasis were similar. Conclusions Postoperative intraperitoneal chemotherapy combined with systemic chemotherapy improves 3-year and 5-year overall survival rates in patients with stage Ⅲ serosa-involved colorectal cancer, and decreases local recurrence, peritoneal metastasis and liver metastasis rate, especially when intraperitoneal chemotherapy regimen contains Oxaliphtin. Comparing with open surgery, laparoscopic surgery dose not improve 3-year and S-year overall survival rates in patients receiving combined chemotherapy or systemic chemotherapy alone.     

Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries. OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats. DESIGN: A randomized controlled animal trial. SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University. MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220–250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point. METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7–10 days. MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively. RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly expressed at 14 and 28 days, but decreased at 60 days, mainly located in the neurons of spinal cord gray matter anterior horn, and they expressed fewer in the motor neurons and white matter of ventral horn, and there were obvious differences between the estrogen-treated group and saline control group at 7, 14, 28 and 60 days (P < 0.05). CONCLUSION: Estrogen can reduce the apoptosis of nerve cells and promote the recovery of neurological function following gradual chronic spinal cord injury.     

Elevated concentrations of CRF in the locus coeruleus of depressed subjects.

Research evidence that corticotropin-releasing factor (CRF) plays a role in the pathophysiology of major depressive disorder (MDD) has accumulated over the past 20 years. The elevation of lumbar cerebrospinal fluid (CSF) concentrations of CRF decreased responsiveness of pituitary CRF receptors to challenge with synthetic CRF, and increased levels of serum cortisol in MDD subjects support the hypothesis that CRF is chronically hypersecreted in at least the endocrine circuits of the hypothalamic-pituitary-adrenal (HPA) axis and may also involve other CRF brain circuits mediating emotional responses and/or arousal. One such circuit includes the excitatory CRF input to the locus coeruleus (LC), the major source of norepinephrine in the brain. Furthermore, there are now reports of decreased levels of CRF in lumbar CSF from MDD patients after symptom relief from chronic treatment with antidepressant drugs or electroconvulsive therapy. Whether this normalization reflects therapeutic effects on both endocrine- and limbic-associated CRF circuits has not yet been effectively addressed. In this brief report, we describe increased concentrations of CRF-like immunoreactivity in micropunches of post-mortem LC from subjects with MDD symptoms as established by retrospective psychiatric diagnosis compared to nondepressed subjects matched for age and sex.