Time Course and Reversibility of Ethanol''s Suppressive Effects on Axon Sprouting in the Dentate Gyrus of the Adult Rat

Ethanol was administered chronically to adult rats in a liquid diet for 14 days preceding and for 5, 7, 8, 9, or 10 days following the unilateral destruction of the entorhinal cortex. Control groups received a diet of lab chow and water and were sacrificed at comparable survival times. An additional experimental group was given ethanol until 9 days after the lesion, then switched to lab chow and water and sacrificed 1 day later. Coronal sections through the dorsal hippocampal formation were stained and analyzed histochemically for the localization of acetylcholinesterase (AChE). Quantitative measurements of the histochemical patterns in the molecular layer of the dentate gyrus were obtained. Ethanol exposure inhibited the withdrawal of the acetylcholinesterase-stained septohippocampal fibers and limited the typical lesion-induced expansion of the pale-staining commissural/associational zone in the molecular layer of the denervated dentate gyrus. However, abstinence from ethanol for just 24 h released the inhibitory effect on the acetylcholinesterase-staining fibers, resulting in a significant expansion of the commissural/associational zone.     

Blood Pressure and Alcohol Intake in Heart Patients

The association between alcohol consumption and blood pressure has been studied in 2025 male and 282 female patients undergoing diagnostic coronary angiography. The increase in amount of alcohol consumed correlated with higher systolic and diastolic blood pressure; this effect was especially pronounced in men over 50 years of age. The association was less marked in male patients under 50 years old, in women, and in patients on antihypertensive medication. Readings in the range of definitive hypertension were more prevalent among older patients consuming six or more drinks daily than in abstainers of the same age group.     

Colonic Surgery With Accelerated Rehabilitation or Conventional Care

BACKGROUND For patients undergoing colonic surgery, the postoperative hospital stay is usually 6 to 10 days, and the morbidity rate is 15 to 20 percent. Fast-track rehabilitation programs have reduced the hospital stay to 2 to 3 days. The aim of this study was to evaluate the postoperative outcome after colonic resection with conventional care compared with fast-track multimodal rehabilitation.METHODS One hundred thirty consecutive patients receiving conventional care (group 1) in one hospital were compared with 130 consecutive patients receiving multimodal, fast-track rehabilitation (group 2) in another hospital. Outcomes were time to first defecation after surgery, postoperative hospital stay, and morbidity during the first postoperative month.RESULTS Median age was 74 years (group 1) and 72 years (group 2). American Society of Anesthesiologists (ASA) score was significantly higher in group 2 (P < 0.05). Defecation occurred on day 4.5 in group 1 and day 2 in group 2 (P < 0.05). Median hospital stay was 8 days in group 1 and 2 days in group 2 (P < 0.05). The use of a nasogastric tube was longer in group 1 (P < 0.05). The overall complication rate (35 patients) was lower in group 2 (P < 0.05), especially cardiopulmonary complications (5 patients; P < 0.01). Readmission was necessary in 12 percent of cases for group 1 and 20 percent in group 2 (P > 0.05).CONCLUSIONS Time to first defecation, hospital stay, and morbidity may be reduced after colonic resection with fast-track multimodal rehabilitation.Reprints are not available.     

Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury

BACKGROUND: Recent studies show that erythropoietin (EPO) plays a protective role in brain ischemia. In this condition, administration of EPO protects neurons from ischemic damage. Recently, it has been shown that in patients with chronic heart failure (CHF), EPO treatment improved cardiac function. In the present study we assessed the role of EPO and EPO-receptor (EPO-R) in the heart. METHODS AND RESULTS: We studied the presence and functionality of the EPO-R in isolated rat hearts in the Langendorff set-up. Hearts were perfused for 20 min with 10 U/ml EPO or vehicle. Immunohistochemistry revealed the presence of the EPO-R on endothelial cells, fibroblasts and to a lesser extent cardiomyocytes. Furthermore, perfusion with EPO resulted in a 50% increase in the phosphorylated MAP kinases p42/p44. To evaluate the protective role of EPO in cardiac ischemia, we performed low-flow (0.6 ml/min) ischemia/reperfusion experiments in isolated rat hearts. Administration of EPO (10 U/ml) reduced the cellular damage by 56% (P<0.05) during reperfusion, diminished apoptosis by 15% (P<0.05) and resulted in a significantly improved recovery of left ventricular pressure (P=0.02) and coronary flow (P=0.01). CONCLUSION: The present data suggest that a functional EPO-R is present in rat adult cardiac tissue and that exogenous EPO administration improves cardiac function after ischemia/reperfusion injury.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as ≥1 stenosis of ≥50% in a major epicardial artery or its main branches; severe coronary disease was defined as ≥50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with ≥70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.     

Reduction in alkaline sphingomyelinase in colorectal tumorigenesis is not related to the APC gene mutation

BACKGROUND AND AIMS. The sphingomyelin pathway is an important intracellular mechanism in regulating cell growth. The first step in this pathway is catalysed by sphingomyelinases. Alkaline sphingomyelinase is specifically located in the intestinal tract. Markedly reduced alkaline sphingomyelinase activities have been found in sporadic colorectal tumours and in familial adenomatous polyposis adenomas. Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations. PATIENTS AND METHODS. Both germline and sporadic adenomatous polyposis coli gene mutations were studied. Alkaline, neutral, and acid sphingomyelinase activities were measured in the intestinal mucosa and content of multiple intestinal neoplasia mice, a murine model of familial adenomatous polyposis and compared to control mice. Alkaline sphingomyelinase activity was also measured in 11 human rectal tumors with APC gene mutation and compared with 9 control tumors without mutation. RESULTS. Alkaline, neutral, and acid sphingomyelinase activities were present in the small intestine and colon in both mice types with no differences in hydrolytic capacity or distribution pattern. In sporadic rectal tumors similar alkaline sphingomyelinase activities were identified in tumors with somatic APC gene mutations as in samples without mutations. In the tumors without detectable APC mutations beta-catenin was analyzed, but no mutation was detected. CONCLUSION. Alkaline sphingomyelinase is not directly linked to adenomatous polyposis coli gene mutations.     

Morphological disruption of colonic mucosa by free or cholestyramine-bound bile acids

In order to assess the effects of free or resin-bound bile acids on colonic topography, adult rats were surgically provided with an indwelling infusion catheter in the proximal cecum, which exited at the neck behind the head. Conscious, unrestrained rats were allowed chowad libitum and were administered 1 ml of an infusion mixture twice daily for five days. The infusion mixtures included either carrier saline, 100 mg cholestyramine, 165 μmol mixed bile acids, or the bile acids bound to cholestyramine. Additional groups of rats were fed defined diets with and without 2% cholestyramine. Compared to fed controls, colonic infusions of saline had little effect on colon topography. Infusions of 100 mg of cholestyramine in saline twice each day did cause some apparent damage to surface morphology of the colon, but not to the extent observed during feeding of the resin as 2% of the diet. In contrast, extensive surface damage of the colon was observed by twice daily infusions of either 165 μmol of an equimolar mixture of cholic, deoxycholic, and chenodeoxycholic acids, or by the bile acids mixed previously with the ion-exchange resin. The data suggest that topographical damage of the colon observed during feeding of bile acid-sequestering resins is in large part due to increased concentrations of either bound or unbound bile acids in the large bowel.