Inhibitory effect of the methanolic extract of Verbascum latisepalum Hub.-Mor. on endothelium-dependent relaxation in rat thoracic aorta.

The leaves and flowers of Verbascum species are used to treat respiratory disorders, haemorrhoids, rheumatic pain, and wounds as well as for the treatment of eczema and other types of inflammatory skin conditions in traditional Turkish medicine. We examined the effect of the methanolic extract of the aerial parts of Verbascum latisepalum Hub.-Mor. on the endothelium-dependent relaxation response in rat aortic rings which is mediated by nitric oxide (NO). Six fractions, A-F, were obtained from the methanolic extract through bioassay-guided fractionation procedures. The phenylethanoid glycoside verbascoside was isolated from fraction D and its structure elucidated by spectral techniques. The inhibitory effects of the extract, its fractions, and verbascoside on the acetylcholine-induced relaxation response in phenylephrine-precontracted aorta was examined in the absence and presence of L-arginine, a precursor in the synthesis of NO. The observation that the effects of the methanolic extract, of fraction D, and of verbascoside were reversed by L-arginine, indicates that verbascoside has an inhibitory effect on the synthesis of NO. This effect should be taken into consideration in view of the wide range of uses of Verbascum species in Turkish folk medicine.

Hydrogen sulfide donors prevent lipopolysaccharide-induced airway hyperreactivity in an in vitro model of chronic inflammation in mice.

We aimed to investigate and compare the effects of rapid (NaHS) and slow (GYY4137 and AP39) hydrogen sulfide (H2 S) releasing donors on LPS-induced tracheal hyperreactivity and pro-inflammatory cytokine levels in lung tissues of mice. Tissues were isolated from male BALB/c mice and incubated with LPS (10 µg/mL) in tissue culture. The subgroups were incubated with NaHS, GYY4137 and mitochondria-targeted donor AP39. LPS incubation did not alter contraction response to carbachol, but enhanced 5-HT and bradykinin-induced contractions in tracheal rings, and elevated IL-1ß, IL-6 and TNF-α levels in lung homogenates. NaHS at 300 µmol/L and 1000 µmol/L, GYY4137 at 30 µmol/L and 100 µmol/L, and AP39 at 30 nmol/L concentrations inhibited the tracheal hyperreactivity to 5-HT, whereas none of these donors affected the enhanced contraction to bradykinin. GYY4137 was also effective to inhibit 5-HT hyperreactivity acutely. In lung tissues, NaHS prevented the elevation of IL-1ß level at 1000 µmol/L, and IL-6 and TNF-α levels at 100 µmol/L concentrations. Incubation with GYY4137 (100 µmol/L) and AP39 (30 nmol/L and 300 nmol/L) inhibited the increase in IL-6 and TNF-α levels, but not IL-1ß at concentrations that they affected tracheal hyperreactivity. These results indicate that H2 S donors can decrease inflammation and prevent airway hyperreactivity.

Effect of exogenous GnRH at the time of artificial insemination on reproductive performance of Awassi ewes synchronized with progestagen-PMSG-PGF2alpha combination.

This study was carried out to investigate the efficacy of PGF(2alpha) for oestrus synchronization (ES) in Awassi ewes to which were administered the progestagen-PMSG combination, and to evaluate the effect of the exogenous GnRH administration immediately after the artificial insemination (AI) on their pregnancy rate and lambing performance during the breeding season. The ewes (n = 33) were treated with an intravaginal sponge impregnated with 30 mg fluorogestane acetate for 12 days and were injected with 500 IU PMSG at the time of removal of the sponge. The ewes were then divided into three equal groups of 11 ewes each. One millilitre of physiological saline (0.9% NaCl; placebo) was administered to each ewe in Group 1 at the time of second AI. Approximately 4 microg GnRH (busereline) was injected to each ewe in Group 2 immediately after second AI. A total of 150 microg PGF(2alpha) (cloprostenole) was injected at the time of sponge removal on day 12 and 4 microg GnRH immediately after the second AI was also treated to each ewe in Group 3. Intracervical AI with diluted fresh semen was performed twice at 12 and 24 h following the onset of oestrus. The injection-oestrus onset and injection-oestrus-end interval in Group 3 was significantly (p < 0.001) shorter than both Groups 1 and 2. Although the pregnancy rates of Groups 2 and 3 (81.8%; 9/11) were numerically higher than of Group 1 (63.6%; 7/11), the difference among the groups was statistically insignificant. The multiple birth rate of Group 3 was found higher than Groups 1 and 2. However, the number of single lambs of Group 1 was also higher than Groups 2 and 3 (p < 0.05). Despite the litter sizes of Groups 2 (1.27; 14/11) and 3 (1.55; 17/11) being numerically higher than Group 1 (0.73; 8/11), the differences among all the groups were statistically insignificant. In conclusion, the administration of PGF(2alpha) at the time of removal of the sponge shortens the injection oestrus-onset and oestrus-end interval in Awassi ewes treated with progestagen-PMSG. Additionally, exogenous GnRH treatment immediately after the AI increases the multiple birth rate of Awassi ewes synchronized with progestagen-PMSG-PGF(2alpha) combination.

[Unclear per anum bleeding during pregnancy]. / Unklare peranale Blutung in der Schwangerschaft.

A 30-year-old, 7-months pregnant woman presented with per anum bleeding. Rectoscopy showed the cause to be a polyp the size of a fingertip 9 cm from the anus. Since the bleeding stopped spontaneously and therefore the need for radical intervention, and due to the advanced pregnancy stage, no biopsy was done. About 1 year later, the same patient experienced sharp pains and anal bleeding during defecation. A poorly defined neuroendocrine carcinoma was diagnosed. Seeking a prognosis optimal for the newborn child, the interdisciplinary decision was made for primary surgery with adjuvant chemotherapy. Other options for this malignancy during and after pregnancy are also discussed.

Ambulatory oesophageal pressure, pH and ECG recording in patients with normal and pathological coronary angiography and intermittent chest pain.

The present study was performed to compare pain-related oesophageal motility, gastro-oesophageal reflux and ST-segment deviations in patients with intermittent chest pain and normal or pathological coronary angiography. Thirty patients (11 males, 19 females; mean age 54.8 years) with normal and 15 patients (12 males, 3 females; mean age 66.7 years) with pathological coronary angiography were investigated by 24-h oesophageal pressure, pH and ECG recording. Chest pain correlated with motility abnormalities or gastro-oesophageal reflux occurred in 33% (10/30) of patients with normal coronary arteries and in 26% of patients with pathological coronary angiography. Symptomatic and asymptomatic ST-segment changes were less frequently observed in patients with normal angiography (4/30) than in patients with pathological coronary angiography (7/14; P = 0.02). Oesophageal dysfunction coincided with ST-segment deviation in 6.7% (2/30) of patients with normal and 40% (6/15) of patients with pathological coronary angiography (P = 0.02). The conclusions reached were: (1) pain-correlated abnormal motility or gastro-oesophageal reflux occurred in patients with normal and pathological coronary angiography at the same frequency; (2) ambulatory motility and pH recording alone does not appear to differentiate between cardiac and non-cardiac chest pain; (3) simultaneous ECG recording reveals a significant correlation of ST-segment deviation and gastro-oesophageal reflux or abnormal motility in patients with coronary artery stenosis.

Long-term clinical outcome of post-cholecystectomy patients with biliary-type pain: results of manometry, non-invasive techniques and endoscopic sphincterotomy.

OBJECTIVE: The purpose of the present study was to investigate prospectively the value of manometry, non-invasive techniques and endoscopic sphincterotomy in biliary type II and III patients with suspected sphincter of Oddi dysfunction. METHODS: All patients (n = 31) had undergone a cholecystectomy from 1 to 45 years before entry into the study, and had a history of biliary-type pain ranging from 4 to 156 months. In a primary diagnostic work-up, including ERCP, other causes of gastrointestinal disease were excluded. The width of the common bile duct, pain induced by the injection of contrast medium into the common bile duct, delayed contrast drainage and the results of a morphine-neostigmine test were analysed. Manometric measurements of basal sphincter of Oddi pressure were performed. Twenty-three patients with an elevated basal pressure (> 40 mmHg) underwent endoscopic sphincterotomy. RESULTS: During the follow-up period (8-62 months) 83% of the patients became symptom free or experienced an improvement. Basal sphincter of Oddi pressure and long-term clinical outcome of patients correlated to different degrees with the results of non-invasive techniques. CONCLUSIONS: Our data suggest that endoscopic sphincterotomy may be an effective therapeutic modality in group II and III patients with sphincter of Oddi dysfunction in whom other gastrointestinal disorders have previously been excluded.

Effects of acetylsalicylic acid and metamizol on hyaluronidase activity and sperm characteristics in rams.

The effects of acetylsalicylic acid and metamizol on hyaluronidase activity of semen and sperm characteristics in rams were investigated. Acetylsalicylic acid and metamizol at the doses of 75 and 50 mg/kg were administered to the rams, respectively and then semen samples were taken at 1, 2, 4, 24, 48, 96, 120 and 144 h. The hyaluronidase activities of semen in rams treated with acetylsalicylic acid and metamizol were determined to increase significantly (P<0.001) when compared with control groups at all times. Additionally, the spermatozoa motilities in both groups were measured to increase significantly (P<0.05) when compared with control group. Furthermore, there were significant (P<0.01, <0.05) decreases in the sperm concentrations and semen volumes of rams treated with acetylsalicylic acid and metamizol at all times, respectively. In conclusion, although the use of acetylsalicylic acid and metamizol cause an increase in the hyaluronidase activities and spermatozoa motilities, these drugs decrease the sperm concentrations and semen volumes along 6 days. For these reason, the use of these drugs in breeding rams during ramming season is not suitable.

Exocrine pancreatic function after recovery from necrotizing pancreatitis.

The aim of the present study was to investigate the exocrine pancreatic function after recovery from necrotizing pancreatitis. The exocrine function was analysed in 53 patients who had recovered from their first attack of necrotizing pancreatitis. In a group of 23 patients (Group A), three follow-up studies were performed between four weeks and 12 months after recovery from acute pancreatitis. A second group of 30 patients (Group B) was submitted to only one function test 18 months after recovery from acute necrotizing pancreatitis. Exocrine pancreatic function was observed after endogenous stimulation using the Lundh test meal. In Group A, after four weeks 74% of the patients had mild-to-moderate insufficiency, while 26% suffered from severe impairment of pancreatic function. Twelve months after recovery, only 16% of the patients showed a normal pancreatic response, while 84% still had pancreatic insufficiency of variable severity. In Group B, 13% of the patients showed a normal pancreatic response, while mild-to-moderate insufficiency was observed in 81%. Severe pancreatic insufficiency was measured only in 6% of these patients. After recovery from necrotizing pancreatitis persistent global or dissociated functional insufficiency is found in 80-85% of the cases. Individual pancreatic enzyme secretion varies quiet considerably during the course of recovery in the follow-up period.

[Diagnostic strategy in constipation, including irritable bowel syndrome]. / Diagnostische Strategie bei Obstipation einschliesslich irritablem Darmsyndrom.

Constipation is not a disease but a symptom. Underlying causes include side effects of drugs, metabolic, endocrine, neurologic, psychiatric and intestinal diseases. Constipation is part of the so-called irritable bowel syndrome. The diagnosis is based on history, physical examination and a few laboratory tests. Second-line diagnostic procedures include endoscopy, colonic transit time and physiological investigations of the anorectum like anorectal manometry or defecography.

Low graft function and ongoing hyperparathyroidism are closely related to post-transplantation osteoporosis.

INTRODUCTION: Renal transplantation (RT) is the gold standard therapy for chronic renal failure. Immunosuppressive drug choice, malnutrition, adynamic bone disease and hyperparathyroidism are important factors impacting the development of posttransplant osteoporosis. Body composition analysis with bioimpedance devices (BIA) is a useful noninvasive tool to detect malnutrition among the RT population. We investigated the effects of graft function, immunosuppressive drug regimens and biochemical characteristics on bone mineral density of RT patients as well as the reliability of BIA measurements to diagnose osteoporosis. METHODS: One hundred three recipients with a minimum of 12 months post-RT follow-up underwent body composition analysis using the Tanita Analyzer. The last 6 months of monthly biochemical parameters and glomerular filtration rates (GFR) as well as drug regimens were collected retrospectively from patient charts. Patients were divided into 2 groups, according to their femoral neck and lumbal T scores, as osteoporosis (n = 42) and control groups (n = 61). RESULTS: The mean GFR of osteoporotic patients was significantly lower (P = .04) and parathyroid hormone (PTH) levels significantly higher (P = .002). According to BIA, osteoporotic patients showed lower bone mass, fat mass, visceral fat ratio, muscle mass, waist-hip ratios, and body mass index values (P < .05). Correlation analysis revealed GFR to negatively correlate with PTH (r = -0.231, P = .010) and positively with femur t scores (r = 0.389, P = .0001) as well as with BIA findings (P = .0001). In contrast, PTH levels in negatively correlated with lumbar and femoral neck t scores (r = -0.22, -0.4 and P = .026, .0001, respectively) but not with BIA findings including bone mass. CONCLUSION: Changes in bone density after RT were affected by graft function. The rapid loss of bone mineral density emphasizes the need for prevention started in the early posttransplant period. BMD measurements provided a guide for treatment and for subsequent evaluation.

Hydrogen sulphide inhibits carbachol-induced contractile responses in ß-escin permeabilized guinea-pig taenia caecum.

Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and ß-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum.

Physiological studies of exocrine pancreatic secretion in conscious rats. 6th communication: steady-state adaptation to different food composition.

In conscious rats provided with appropriate indwelling catheters the steady-state adaptation of digestive enzymes in pancreatic juice is investigated in relation to different food composition. Six isocaloric diets with different composition of carbohydrates (5-70%), proteins (10-57%) and fat (0-38%) are applied for two weeks before operation and also afterwards. The parameters determined are: flow-rate and total protein concentration of pancreatic juice, enzyme-separation by PAA-Gel-Electrophoresis and quantitative analysis of amylases I and II, lipase, chymotrypsins I and II and trypsin. The specific enzymatic activity, characterized by the enzyme fraction in per cent of total protein can be described best as a linear function of the corresponding nutrient portion (%) in the food. (Coefficient of linear regression mostly r = 0.98%). The regression lines for the sum of both amylases and all proteases are parallel to each other (y = 0.45x + b). Lipase activity is also linearly increasing with fat in food having a much smaller slope (y = 0.16x + b). The regression lines (y = ax + b) intersect with the ordinate at different points (section b), characterizing the "basal" secretion of pancreatic enzymes without any substrate in food. b (in %) for amylase I = 3.14, amylase II = 0.7 !, total proteases = 12.5 and lipase = 13.6. The regularity of inherent laws governing adaptation of pancreatic enzyme production and secretion to food composition allow to predict the prospective enzymatic secretion pattern for any given food composition.

Ultrasonography as a primary diagnostic tool in patients with inflammatory disease and tumors of the small intestine and large bowel.

In 240 patients with predefined indications, the validity of ultrasound imaging as a primary diagnostic procedure was examined prospectively. Ultrasonography revealed normal intestinal findings in 150 patients and pathological lesions in 90 subjects. All patients underwent subsequent endoscopic, radiological, or surgical examination. In 7 patients with Crohn's disease and in 2 patients with radiation colitis, the ultrasound findings were false-negative. In the other 9 cases, ultrasonography suggested false-positive results. Ultrasonographic examination of the small intestine and large bowel had a very high overall validity, with a sensitivity of 90% and specificity of 94%.

Physiological studies of exocrine pancreatic secretion in conscious rats. 7th communication: short-term kinetics of adaptation of digestive enzymes to different nutritional stimuli.

In conscious rats provided with appropriate indwelling catheters the kinetic period of adaptation (short-term adaptation) of digestive enzymes was investigated in response to a rapid change of diet and to intraduodenal infusions of different food components. Flow-rate and total protein concentration of pancreatic juice were measured. Enzyme-separation by PAA-Gel-Electrophoresis and quantitative analysis of amylases I and II, lipase, chymotrypsins I and II and trypsin were performed. The specific enzymatic activity was characterized by the enzyme fraction in percent of total protein. Rapid "change of diet" in rats, previously adapted for two weeks to a certain diet, caused increasing and decreasing concentrations of the corresponding enzymes respectively. The kinetic of this adaptation could well be described by exponential functions. Intraduodenal perfusion of starch, soy-bean oil or amino acids revealed similar changes in enzyme secretion as seen in the dietary experiments; i. e. intraduodenaL perfusion of starch caused mainly an increase in amylase secretion, soy-bean oil in lipase secretion and amino acids in the secretion of proteases. The kinetics could be described as a definite transfer function to a rectangular stimulus. The time lag between the duodenal "stimulation" and "response" in pancreatic enzyme secretion was only a few hours. After a period of rapid change in enzyme secretion during the initial 5 hours, the secretion rises more slowly to reach steady-state level after 18-22 hours. The results of this study allow a more detailed formal description of the kinetics of pancreatic short-term adaptation to nutritional stimuli without clarifying the involved mechanisms.

Physiological studies of exocrine pancreatic secretion in conscious rats. 2. Communication: recovery of the animals after operation.

1. In conscious rats provided with indwelling pancreatic and biliary catheters, the postoperative recovery period is investigated. 2. Immediately after operation, serum amylase and lipase concentrations are highly elevated, declining afterwards rapidly and normalizing within 4 days. 3. Food intake, protein secretion and flow rate of the pancreatic juice show an increasing pattern during the first 4-5 days after operation. 4. The amount of secreted protein is a logarithmic function of the amount of food ingested. 5. The spectrum of secreted enzymes shows typical changes after operation, the total sum of relative enzyme fractions remaining constant. 6. The recovery period of rats provided with a pancreatic fistula -- as described previously -- lasts 4-5 days.

Volume and enzyme kinetics of human pancreatic secretion after endogenous stimulation with the Lundh test meal.

The present study was undertaken to investigate the volume and enzyme kinetics of human pancreatic secretion, after endogenous stimulation with a Lundh test meal, and evaluate the most reliable enzyme and collection period. The prestimulatory volume rates did not differentiate normal from pathologic pancreatic function. After ingestion of the test meal, the immediate increase in volume secretion was identical in healthy subjects and patients with pancreatic insufficiency. The latter showed a drastic reduction of prestimulatory and postprandial enzyme secretion. Cimetidine taken orally 12 and 2 h before the test meal study had no effect on volume and enzyme secretion and endogenous CCK release. Especially in severe pancreatic insufficiency, this modification simplified the performance of the Lundh test. The estimation of lipase and trypsin gave a significant correlation between Lundh test and secretin-cerulein test. The endogenous stimulation by Lundh test meal is a reliable test for routine diagnostic and scientific purposes.

Effect of atropine on intestinal phase of pancreatic secretion in man.

The effect of atropine on prestimulatory and Lundh-meal-stimulated pancreatic secretion and on plasma cholecystokinin (CCK) levels has been studied in 20 human volunteers. Prestimulatory secretion was lowered by infusion of atropine. From 10 to 30 min after ingestion of the Lundh meal, atropine had no effect on secretion. From 30 to 120 min, the stimulated enzyme secretion was reduced by 90% during infusion of atropine. Plasma CCK levels were not altered by atropine. Similar results were obtained when the test meal was instilled into the duodenum to exclude a delay of gastric emptying caused by atropine. These data show that cholinergic blockade does not interfere with CCK-mediated stimulation of pancreatic secretion during the first 30 min after ingestion of a meal, and that afterwards the intestinal phase is mainly under cholinergic control.

Endoscopic management of malignant biliary obstruction and recurrent cholangitis with a self-expanding prosthesis.

Endoscopic implantation of a prosthesis usually provides effective palliation in malignant biliary obstruction and in some cases of benign strictures. The most common problem concerning stent patency is occlusion, which may lead on to cholangitis and septic complications. A new technique employing self-expanding stents offers encouraging results. Preliminary clinical experience with expanding biliary stents are reported. The expectations of the doctor and patient, and the preferences and advantages of this new method are discussed on the basis of a case report with recurrent septic complications caused by conventional biliary prosthesis.

[Percutaneous sonographically guided fine-needle puncture and drainage of pyogenic abscesses]. / Perkutane, sonographisch gesteuerte Feinnadelpunktion und Drainage pyogener Abszesse.

Between January 1988 and April 1991, a total of 79 ultrasound-directed percutaneous punctures and (or) drainage of abscesses were performed on 31 patients (15 men, 16 women; mean age 63 [31-85] years). There were 14 hepatic, 4 splenic, 4 abdominal wall and 3 pancreatic abscesses, and one each subphrenic, presacral, retrocaecal, ischiorectal, pulmonary and in the psoas. After ultrasound localization of the abscess a fine-needle puncture was performed, after which the abscess cavity was emptied as much as possible or, in abscesses larger than 5 cm in diameter, drained through a pig-tail catheter (6-8, 4 F). Several punctures were needed in 16 patients, while in 15 a percutaneous drainage over 2-8 days was necessary. Treatment was successful after 4-17 days in 25 patients. One patient died in septic shock. Operative intervention after diagnostic puncture was undertaken in 5 patients. There were no complications related to the method. In 11 patients the further course was determined by an underlying malignant disease. No recurrence has been noted (4-36 months after treatment) in 14 patients with a benign underlying disease. Percutaneous puncture and drainage of pyogenic abscesses is a technically simple method which achieves good results.