Activity of type IV collagenases (MMP-2 and MMP-9) in primary pulmonary carcinomas: a quantitative analysis

PURPOSE: Matrix metalloproteinases MMP-2 and MMP-9 are implicated in invasion and metastasis of malignant tumors. We investigated the expression and activation of MMP-2 and MMP-9 in lung cancer compared with normal lung parenchyma, and looked for a potential marker of malignancy. METHODS: Thirty-six pulmonary carcinomas and paired normal lung specimens were analyzed by gelatin zymography and computer-assisted image analysis for the expression of MMP-2 and MMP-9. RESULTS: We showed that expression of both type IV collagenases was remarkably higher in carcinoma samples than in lung parenchyma. The MMP-9 levels in lung cancer were over twofold higher than in normal lung tissues. The levels of latent and active forms of MMP-2 in lung cancer samples were, correspondingly, 3.8- and 17-fold higher than in lung parenchyma. The tumor/normal (T/N) ratios of MMP-2 were negatively correlated with the hemoglobin levels and erythrocytes number. CONCLUSIONS: A high level of the active form of MMP-2 in almost all of the carcinomas and the near lack of its activation in normal lung parenchyma shows that MMP-2 activation is associated with the malignant phenotype and may serve as a good marker of malignancy. The correlation between low hemoglobin level and T/N ratio of MMP-2 may indicate significance of MMP-2 for angiogenesis.     

Outcome of Colectomy for Slow-Transit Constipation in Relation to Presence of Small-Bowel Dysmotility

PURPOSE: A significant proportion of patients with slow-transit constipation have abnormal small-bowel motility. It is unclear whether abnormal small-bowel motility indicates worse results after surgery for slow-transit constipation. We studied the results of colectomy with ileorectal anastomosis in patients with normal and abnormal antroduodenal manometry findings. METHODS: Seventeen, consecutive patients who had been referred for intractable constipation and who were found to suffer from slow-transit constipation underwent subtotal colectomy. All patients underwent a set of diagnostic investigations, including whole gut transit time, anorectal manometry, antroduodenal manometry, electromyography of the anal sphincter, balloon expulsion test, and defecography. Patients were followed up after five years. RESULTS: Patients median age at the time of the operation was 46 (range, 23–70) years, and the median duration of constipation was 31 (range, 11–65) years. One patient died 21 days after the operation. Three patients developed intestinal pseudo-obstruction after the operation, and two of these died during the follow-up period. Fourteen patients were available for follow-up after a median of five (range, 4–7) years. Bowel frequency was significantly increased from a median of 0 (range, 0–2) times per week to a median of 30 (range, 10–102) times per week after surgery (P < 0.001). The incidence of abdominal pain decreased from 94 to 43 percent. Seven of 13 patients (54 percent) continued to have bloating. At long-term follow-up, 12 of 14 patients (86 percent) reported that they had an overall improvement after surgery, despite continuing pain and bloating in a significant proportion of them. The outcome of surgery was good or excellent in seven of seven patients with normal findings on antroduodenal manometry, but only five of nine patients with abnormal manometry findings attained a good result after surgery. We found a trend (P = 0.09) toward better long-term results after surgery for slow-transit constipation in patients with a normal antroduodenal manometry before the operation.     

Clinical value of symptom assessment in patients with constipation

PURPOSE: This study was designed to evaluate symptoms and clinical findings in a prospective series of patients with chronic constipation. METHODS: A total of 155 consecutive patients with intractable constipation underwent detailed symptom registration, anorectal manometry, electromyography, colonic transit time measurement, and defecography. RESULTS: All investigations were completed by 134 patients (112 females) with a median age of 52 (range, 17–79) years. Whole-gut transit time was delayed in 55 patients (41 percent), pelvic floor dysfunction was diagnosed in 59 patients (44 percent), but in 35 percent of patients both transit time and pelvic floor function were found to be normal. Three symptoms were shown to have an independent value for the diagnosis of slow-transit constipation. Patients with slow transit more often reported two or fewer stools per week (84vs. 46 percent), laxative dependence (87vs. 44 percent), and a history of constipation since childhood (58vs. 22 percent) than did those with normal transit. Pelvic floor dysfunction was associated with a higher prevalence of backache (53vs. 33 percent) and a lower prevalence of normal stool frequency (19vs. 36 percent), heartburn (12vs. 27 percent), and a history of anorectal surgery (7vs. 21 percent) compared with those with normal pelvic floor function. All four symptoms retained an independent value in the logistic regression analysis for pelvic floor dysfunction. Two symptoms characterized the group with normal transit and normal pelvic floor function: normal stool frequency and alternating diarrhea and constipation. CONCLUSIONS: Symptoms are good predictors of transit time but poorer predictors of pelvic floor function in patients with constipation.     

Physiology of renal sodium transport

A wealth of studies performed with a spectrum of methods spanning simple clearance studies to the molecular identification of ion transporters has increased our understanding of how approximately 1.7 kg of NaCl and 180 L of H2O are absorbed by renal tubules in man and how the urinary excretion is fine-tuned to meet homeostatic requirements. This review will summarize our current understanding. In the proximal nephron, approximately 60 to 70% of the filtered Na+ and H2O is absorbed together with approximately 90% of the filtered HCO3-. The exact quantities are determined by many regulatory factors, such as glomerulotubular balance, angiotensin II, endothelin, sympathetic innervation, parathyroid hormone, dopamine, acid base status and others. The essential components of absorption are luminal membrane Na+/H+ exchange and the basolateral (Na+ + K+)-ATPase. In the thick ascending limb of the loop of Henle, 20 to 30% of the filtered NaCl is absorbed via Na+2Cl-K+ cotransport driven by the basolateral (Na+ + K+)-ATPase. No H2O is absorbed at this nephron site. The transport rate is determined by the Na+ load and by several hormones and neurotransmitters, including prostaglandins, parathyroid hormone, glucagon, calcitonin, arginine vasopressin (AVP), and adrenaline. In the distal tubule, some 5 to 10% of the filtered load is absorbed via Na+Cl- cotransport in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. The rate of transport is again determined by the delivered load and by several hormones and neurotransmitters. One of the tasks of the collecting duct is to control the absorption of approximately 10 to 15% of the filtered H2O, regulated by AVP, and just a few percent of the filtered Na+, controlled by aldosterone and natriuretic hormone. The water absorption proceeds through the luminal membrane via aquaporin 2 and through the basolateral membrane via aquaporin 3 channels and is driven by the osmotic gradient built up by the counter current concentrating system. The Na+ absorption occurs via Na+ channels present in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. With no pharmacological interference, urinary excretion of Na+ can vary between less than 0.1% and no more than 3% of the filtered load, and that of H2O can vary between 0.3 and 15%.     

Recovery of muscle strength after microdiscectomy for lumbar disc herniation: a prospective cohort study with 1-year follow-up

Background  

Surgery has not been proven to be a better treatment option than non-operative management for limb paresis due to lumbar disc herniation. For the patients it will still be a concern, whether they will regain full strength after the operation or not.     

Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells. Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed the strongest growth inhibition with an IC₅₀ of 1.9±0.5 µg followed by epiashantin (IC₅₀=9.8±4.5 µM) and arctigenin (IC₅₀=16.5±8.5 µM). The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl_xl and an increase of the apoptotic index. The time interval until loss of MMP and down modulation of bcl_xl became evident correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl₂ and caspase 3 were not involved. NDGA also induced a shift of the culture population to the G₂/M phase of the cell cycle. With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention of colorectal tumors.     

Retention of aluminium in the tissues of rats after the discontinuation of oral exposure to aluminium

Two studies were conducted to determine whether the aluminium deposited in the bones, muscles and kidneys of young growing rats fed diets supplemented with A1(OH)₃ (989 or 1070 μg A1/g diet) for 16 days was retained after the A1(OH)₃ was removed from the diets. Al levels in the tissues of test rats decreased significantly (P 0.01) 3 days after withdrawal of the Al(OH)₃ from the diet, and 7 days after withdrawal the tissue concentrations of A1 were similar in the test and control animals. Ingestion of A1 had no effect on tissue levels of phosphorus, calcium, magnesium, zinc or iron.