Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65.

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory.

Multiple imaging findings in SAPHO syndrome.

SAPHO syndrome is an acronym for a clinical entity characterized by synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis. The association of sterile inflammatory bone lesions and neutrophilic skin eruptions is indicative of this syndrome, even though not all components always coexist. We report a case of a 62-year-old female presenting with a lytic manubrial lesion. Diagnoses of metastasis or infection were initially entertained but excluded on open biopsy, and SAPHO syndrome was confirmed on additional investigation and follow-up. Striking imaging findings included intense uptake on bone scintigraphy, photopenia on white blood cell imaging, and dramatically elevated lumbar spine bone density on dual energy x-ray absorptiometry (DXA).

Surfactant protein D: a lung specific biomarker in COPD?

A major impediment in the development of novel drugs for chronic obstructive pulmonary disease (COPD) has been the scarcity of a well-validated, robust, and easily obtainable intermediate end point such as serum biomarkers. To date the best serum biomarkers in COPD have been non-speci"c pro-in"ammatory molecules synthesized largely by extra-pulmonary organs. In COPD, an ideal biomarker would be one that (1) was produced mostly in the lungs (and was reliably measurable in the peripheral circulation using commercially available kits), (2) changed with the clinical status of patients or with relevant exposures; and (3) had inherent functional attributes that suggested a possible causal role in the pathogenesis of the disease. In this paper, we review one promising systemic biomarker that ful"lls some of these criteria, surfactant protein D (SPD).

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia.

BACKGROUND: The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization. RESULTS: Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. CONCLUSION: The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.

Coronary artery aneurysm: a review.

Coronary artery ectasia (CAE) is found in 0.3-5% of patients undergoing coronary angiography. Atherosclerosis is the main cause, followed by Kawasaki disease and infectious emboli. The exact pathogenesis has not been diagnosed as yet, but an inflammatory process is underlying. Symptoms, if present, are usually related to myocardial ischemia. Angiography is the mainstay for diagnosis. The prognosis is generally favorable. Thromboembolic complications are rare with antiplatelet therapy, and spontaneous rupture generally is rare but occurs more commonly in Kawasaki disease. Management varies from antithrombotic therapy to surgical ligation. Controlling coronary heart disease risk factors sharply affects the prognosis in patients with CAE.

Kidney transplantation procedures in rats: assessments, complications, and management.

Kidney transplantation in rats is an experimental model often used for the development of general microsurgical or transplantation techniques, for immunologic studies, and for analyzing transplant-associated long-term arterial blood-pressure changes. The aim of the present study was to analyze different surgical techniques of kidney transplantation in rats, with emphasis on minimizing surgical complications and establishing guidelines for their prevention and management. Complications were categorized into general (e.g., core body temperature drop, ischemic time) and surgically related vascular and urinary tract complications. In conclusion, a significant reduction of the complication rate in renal transplantation in rats can be achieved by placing the animal on a heating pad at an appropriate temperature. To reduce the risk of vascular thrombosis, ice-cold saline with heparin and careful flushing of the donor kidneys are recommended. Vascular complications can be avoided by performing "end-to-end" anastomosis techniques. The use of stents and cannulas in the urinary tract is associated with a high risk of urinary tract obstruction, and therefore is not recommended.

Parathyroid carcinoma: A rare case with mandibular brown tumor.

Parathyroid carcinoma constitutes less than 1 % of primary hyperparathyroidism. The male to female ratio is approximately equal and the mean age at presentation is 40 years. In about half of the patients there is a palpable cervical mass, and serum calcium level is usually above 14 mg/dl. In a case report we present a 21-year-old man with a non-tender, non-mobile bulging mandibular mass. He suffered from fatigue, recent weight loss, hoarseness, polydipsia, polyuria, hematuria, recurrent renal stones and bouts of constipation and diarrhea. A mandibular biopsy confirmed brown tumor. Serum calcium level was 15.4 mg/dl. Cervical ultrasound revealed a hypoecho area suspicious of parathyroid adenoma. Parathyroid carcinoma was later confirmed and en bloc resection was performed. During a two-year follow up there has been no evidence of recurrence or hypercalcemia. This unique case of parathyroid carcinoma in conjunction with brown tumor is the second reported case worldwide.

The epidemiology and clinical findings of colorectal cancer in Iran.

BACKGROUND: This study was performed to evaluate the prevalence, clinical features and management of patients with colorectal cancer (CRC) in Iran. METHODS: All cases of CRC presented to a principal referral University hospital (SGH) for cancers in Teheran, Iran between June 20, 2000 and January 3, 2003 were retrospectively reviewed. RESULTS: A total of 200 patients were included. 114 patients (57%) were male and 86 were female (43%). Age ranged from 13-90 years with a mean of 55.15 +/- 14.5. Among these patients, 16.5% were less than 40 years of age. The tumors were categorized according to their distribution as appendix (n=4), cecum ( n=7), right colon (n=1), hepatic flexure (n=2), transverse colon (n=19), splenic flexure (n=3), left colon (n=6), sigmoid ( n=16), rectum (n=117), rectosigmoid and rectal lesions (n=16), and colorectal lesions without known locations (n=9). Non-mucinous adenocarcinoma (AC) was the most common histological type (n=181, 90%), followed by mucinous AC (n=15), squamous cell carcinoma (n=1), carcinoid (n=1), melanoma (n=1) and signet ring carcinoma (n=1). The most common presenting symptom was rectal bleeding (n=68, 34.5%). Younger patients had a greater preponderance of mucinous AC (p=0.008) and generally underwent more extensive chemotherapy as seen with more usage of 5-Fluorouracil (p=0.05). CONCLUSIONS: We have had few reports with reference to the epidemiology of CRC in Iran since 1977. The current data suggest a younger age distribution for CRC. We found no significant difference between age, gender and type of cancer with subsite distribution. Distal CRC was more prevalent. Among patients, 30.5% were diagnosed by screening studies.

Goblet cell carcinoid of the appendix.

BACKGROUND: Goblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management. METHODS: Published studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix. RESULTS: Based on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation. CONCLUSION: GCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.

Different impact of normo- and hypotensive brain death on renal macro- and microperfusion--an experimental evaluation in a porcine model.

BACKGROUND: Despite the growing use of kidneys from living donors, organs harvested from brain dead donors are the dominant graft types used in renal transplantation. It is accepted that brain death (BD) has a damaging effect on the renal allograft, with a lower graft survival. Amongst various causes, changes in renal microperfusion could be responsible. Renocortical microperfusion was assessed during BD using thermal diffusion in a porcine model. METHODS: Two types of BD were induced in two groups of pigs [hypotension (Hypo-BD): n = 11; normotension (Normo-BD): n = 10] and compared to controls (n = 5) over a period of 210 min. We analysed systemic parameters [heart rate (HR), mean arterial blood pressure (MAP)], aortic blood flow (ABF) and renal perfusion [renal artery blood flow (RABF) and renocortical blood flow (RCBF)]. RESULTS: Following the two distinct forms of BD induction, a stable normo- or hypotension was observed. Haemodynamic parameters were only slightly changed (control group: MAP, 62+/-2 mmHg; HR, 95+/-3/min; Normo-BD: MAP, 56+/-4 mmHg; HR, 104+/-8/min; Hypo-BD: MAP, 43+/-3 mmHg; HR, 112+/-7/min). Solely dependent on systemic haemodynamics, RABF and RCBF decreased in the Hypo-BD (RABF: 142+/-19 to 94+/-9 ml/100 g/min; RCBF: 80+/-4 to 52+/-2 ml/100 g/min), while in Normo-BD group RABF mildly changed (158+/-13 ml/100 g/min) and RCBF decreased slightly from 76+/-3 to 70+/-6 ml/100 g/min. As opposed to the Normo-BD group, animals with Hypo-BD showed a significant decrease in RABF (reduction of 34%) and RCBF (reduction of 35%) with a sharp drop of MAP (reduction of 25%), however ABF remained relatively constant. CONCLUSIONS: In this model, a reduction of renocortical microperfusion in brain dead pigs was only found during haemodynamic instability (hypotension) and could not be attributed to BD as such. Our findings would support intensive cardiocirculatory stabilization for potential BD donors in order to minimize kidney preservation damage.