(-)-Epigallocatechin Gallate Inhibits the Pacemaker Activity of Interstitial Cells of Cajal of Mouse Small Intestine

The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of cultured interstitial cells of Cajal (ICC) from murine small intestine were investigated using whole-cell patch-clamp technique at 30℃ and Ca²⁺ image analysis. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of EGCG. EGCG-induced effects on pacemaker currents were not inhibited by glibenclamide, an ATP-sensitive K⁺ channel blocker and TEA, a Ca²⁺-activated K⁺ channel blocker. Also, we found that EGCG inhibited the spontaneous [Ca²⁺]_i oscillations in cultured ICC. In conclusion, EGCG inhibited the pacemaker activity of ICC and reduced [Ca²⁺]_i oscillations by cAMP-, cGMP-, ATP-sensitive K+ channel-independent manner.     

Evaluation of behavioural and antioxidant activity of <Emphasis Type="Italic">Cytisus scoparius</Emphasis> Link in rats exposed to chronic unpredictable mild stress

Background  

Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS) Link, (Family: Leguminosae), also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.     

Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact on survival

BACKGROUND: The application of CT imaging has increased the identification of patients with clinical T1N0 (cT1N0) lung cancer. The optimal management strategy for these early stage lung cancers remains unclear. We analyzed the impact of occult nodal metastasis on cT1N0 lung cancer patients. METHODS: We studied patients with cT1N0 lung cancer enrolled in our database from January 1995 to December 2002. Preoperative staging was confirmed by review of CT and PET scan studies. Pathology specimens were reviewed. Multivariate analysis was performed to determine the risk of occult nodal involvement. Kaplan-Meier method was applied to analyze survival. RESULTS: Two hundred and ninety-seven patients with cT1N0 disease were identified. Fifty-eight percent of patients were pathological T1N0. Overall, 15% of patients had occult nodal metastasis. Logistic regression analysis demonstrated a three-fold increase in the risk of having pathologic stage II or stage III disease with every 1.0 cm increase in tumor size (odds ratio 3.2; 95% CI: 2.3-4.6). Multivariate analysis demonstrated tumor size to be a significant predictor of nodal metastasis (adjusted odds ratio 3.5; 95% CI: 2.4-5.1). Median survival was different between pathological stage I (96.3 months), stage II (41.4 months), and stage III (36.1 months) disease (p=0.002). CONCLUSION: Clinical T1N0 tumors are often understaged. The risk of occult nodal disease increases with tumor size, and this occult disease negatively impacts survival. Because of the limitations of clinical staging, we believe that lobectomy and lymph node analysis should be offered to cT1N0 lung cancer patients to provide accurate staging and to optimize multimodality adjuvant treatment of lung cancer.     

Pharmacological preconditioning by milrinone: Memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice

We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 μg/kg & 100 μg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.     

Which is more nephrotoxic for kidney transplants: BK nephropathy or rejection?

Little data exist comparing outcomes following BK nephropathy (BKN) vs acute rejection. We reviewed outcomes among recipients who had a primary diagnosis of biopsy‐proven BKN or rejection between 1 and 18 months post‐transplant. There were 96 cases of BKN and 256 cases of rejections. We compared outcomes of BKN with all rejection combined and also with cellular rejection. Seven of 256 (2.7%) patients developed BKN after treatment of rejection. Conversely, 8 of 96 (8.3%) developed rejection after BKN. The eGFR at time of diagnosis in the BKN group (33.7 ± 12.6) was lower than the rejection group (44.8 ± 23.3, P < .001). The eGFR at 6 months after diagnosis of BKN was 32.7 ± 14.9 and for rejection was 48.8 ± 20.7 (P ≤ .001). The mean eGFR at 3 years postdiagnosis was 41.6 ± 18.5 in BKN and 53 ± 21.3 for rejection (P = .001). The graft failure incidence rates were similar between 2 groups. A similar pattern was observed comparing BKN with cellular rejection. While the difference in rate of graft loss between BKN and rejection did not reach statistical significance, kidney function up to 3 years after diagnosis was worse for BKN than for rejection, suggesting that BKN is at least as damaging to kidneys as rejection.     

Excitation patterns in three-dimensional electrical impedance tomography

Electrical impedance tomography (EIT) is a non-invasive technique that aims to reconstruct images of internal electrical properties of a domain, based on electrical measurements on the periphery. Improvements in instrumentation and numerical modeling have led to three-dimensional (3D) imaging. The availability of 3D modeling and imaging raises the question of identifying the best possible excitation patterns that will yield to data, which can be used to produce the best image reconstruction of internal properties. In this work, we describe our 3D finite element model of EIT. Through singular value decomposition as well as examples of reconstructed images, we show that for a homogenous female breast model with four layers of electrodes, a driving pattern where each excitation plane is a sinusoidal pattern out-of-phase with its neighboring plane produces better qualitative images. However, in terms of quantitative imaging an excitation pattern where all electrode layers are in phase produces better results.     

Anastomotic compression button: A new mechanical device for sutureless bowel anastomosis

The anastomotic compression button is a new mechanical device that uses three interlocking polypropylene buttons to produce a sutureless bowel anastomosis. The device is unique in that it allows application of the buttons via a device similar to the popular intraluminal stapler, but it leaves no staples or foreign body of any kind in the bowel wall. The authors compared the 25-mm anastomotic compression button with the 25-mm intraluminal stapler in the colon of dogs. After 28 days, the mucosal blood flow, burst pressure, and anastomotic indices were found to be identical between the anastomotic compression button and the stapler. The anastomotic compression button was easier to use, and microscopic examination showed less ulceration, fibrosis, and inflammation, and better re-epithelialization at the anastomotic compression button site. The anastomotic compression button appears to have the potential to be a superior method compared with stapled anastomoses in the colon.Supported by Deknatel, A Division of Pfizer Incorporated, Fall River, Massachusetts.     

Comparison of the hematopoietic activity of flt-3 ligand and granulocyte-macrophage colony-stimulating factor acting alone or in combination

The hematopoietic sequelae of intramuscular administration of flt-3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone, or in combination, were compared in BALB/c mice. Changes in hematopoiesis were measured in the marrow, spleen and blood using an in vitro colony-forming unit (CFU) assay and flow cytometrically (expression of CD34 and stem cell antigen (Sca)-1). FL administration was associated with a significant increase in the absolute number of CFU and CD34+ cells in the marrow and CFU, CD34+, Sca-1+, and CD34+ Sca-1+ cells in the spleen and blood. These data demonstrate that FL expands and mobilizes a range of hematopoietic progenitors. By comparison, GM-CSF administration was associated with a significant increase in the number of CFU in the spleen and a significant reduction in marrow CD34+, Sca-1+, and CD34+Sca-1+ cells. These data suggest that GM-CSF-driven expansion of CFU may be at the expense of more primitive cells. The pattern of progenitor cell expansion associated with FL + GM-CSF administration was similar to that of FL alone with the following exceptions. The numbers of spleen and blood CFU were significantly greater and the number of marrow CD34+Sca-1+ cells were significantly less, than with FL alone. These data suggest that co-administration of these cytokines may combine the expansion of the more primitive cell populations (associated with FL) with the expansion of the more mature CFU population (associated with GM-CSF) to yield a greater overall CFU expansion and elevation of CFU in the blood. However, increasing the expansion and mobilization of the relatively mature, rather than the more primitive, hematopoietic progenitors, may be of limited value as a mobilization strategy, if the goal is the expansion and isolation of increased numbers of "high-quality," primitive cells for transplantation.     

Laparoscopic Cholecystectomy In Situs Inversus—Our Experience of 6 Cases

Laparoscopic cholecystectomy is the standard procedure for symptomatic gall stone disease. Situs inversus is a condition where the visceral anatomy is reversed. Laparoscopic cholecystectomy in a patient of situs inversus is a technically difficult procedure. Six patients of situs inversus underwent laparoscopic cholecystectomy from January 2003 to December 2009. In the first patient of situs inversus, we operated by placing the ports in mirror image fashion as that of standard laparoscopic cholecystectomy. However in next five patients we modified the technique by interchanging the epigastric and left mid clavicular line ports to overcome the problem of handedness. The procedure was successfully completed in all six patients. No intraoperative or postoperative complications occurred. The mean operating time was 65 mins (45–85 mins). Laparoscopic cholecystectomy is safe in patients of situs inversus. However, extreme care and skill is required to identify the reversed anatomy and to overcome the problem of handedness. Interchanging the epigastric and left mid clavicular line ports makes the procedure easier.     

Modulation of src-kinase attenuates naloxone-precipitated opioid withdrawal syndrome in mice

This study was designed to investigate the effect of 2,3-dihydro-N, N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide (SU-6656), a selective inhibitor of src family kinase, on the development of naloxone-induced opioid withdrawal syndrome in mice. Subacute morphine administration followed by a single injection of naloxone (8 mg/kg, intraperitoneally) was used to precipitate the opioid withdrawal syndrome in mice. Behavioral observations were made immediately after naloxone treatment. The withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and frequency of jumping, rearing, forepaw licking, and circling. Daily single administration of SU-6656 was continued during the morphine treatment procedure. Injection of naloxone precipitated severe withdrawal in morphine-dependent mice. However, once-daily administration of SU-6656 (1.5, 3, and 6 mg/kg, intraperitoneally) markedly and dose-dependently attenuated the naloxone-induced morphine withdrawal syndrome. Therefore, it seems that an src family-kinase-linked mechanism is involved in the development of physiological opioid dependence; thus, src family kinase may serve as a potential target to address the pathological condition of physiological dependence and abstinence associated with continuous opioid usage.