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.

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.

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.

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.

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.

[Diverticulosis and diverticulitis in the elderly]. / Divertikulose und Divertikulitis beim alten Menschen.

Diverticulosis of the colon is a disease that mainly affects the elderly, presenting in 10 to 20% of this age group. The most common complication--painful diverticular disease, is usually treated conservatively with a high-fiber diet, intermittent use of antispasmodics and possibly regulation of the stools. Diagnostic differentiation is best performed using ultrasonography of the bowel wall, supplemented where necessary by computer tomography and colonoscopy (sigmoidoscopy) or, where this latter is not possible, barium enema using Gastrografin. Conservative treatment of diverticulitis with antibiotics, bowel rest, possibly including parenteral alimentation, is usually applied for three to ten days. In the absence of a response to this treatment, frequent recurrence, immunosuppression or complications (perforation, peritonitis, enterovesicular fistula), surgery is indicated.

Treatment of bleeding esophageal varices with cyanoacrylate and polidocanol, or polidocanol alone: results of a prospective study in an unselected group of patients with cirrhosis of the liver.

BACKGROUND AND STUDY AIMS: Data concerning the results with emergency and further elective therapy of esophageal varices using polidocanol and cyanoacrylate, or polidecanol alone, in an unselected group of patients with liver cirrhosis have not previously been available. The aim of the present prospective study was to evaluate acute and repeated cyanoacrylate and polidocanol therapy in the emergency and long-term elective management of esophageal varices. METHODS: In accordance with the protocol of the present prospective study, acutely bleeding esophageal varices of grades 1 to 3 were treated endoscopically with polidocanol injection, while grade 4 varices, large solitary varices (over 5 mm) and otherwise uncontrollable cases of variceal bleeding were treated by injection of cyanoacrylate and polidocanol. Over a period of 62 months, 112 patients (65 men, 47 women) with acute bleeding from esophageal varices due to cirrhosis of the liver (69% alcohol-related) underwent a total of 245 treatment sessions in hospital. The average age of the patients was 62.0 +/- 12.3 years (58.1% were 60 or older). Hepatic function corresponded to Child-Pugh class A in 38 patients (33.9%), Child-Pugh class B in 68 patients (60.7%), and Child-Pugh class C in six (4.5%). RESULTS: Sixty-eight patients (60.7%) were treated with polidocanol alone, and 44 (39.3%) with cyanoacrylate and polidocanol. Acute hemostasis was achieved in all cases. In 5.7% of the sclerotherapy procedures, bleeding ulcers were observed, and a pleural effusion was seen in one case. The hospital mortality rate was 24.1%, resulting from the bleeding in 2.7% and due to liver failure in the remaining cases. Recurrent bleeding occurred within 24 hours in four patients (3.6%), and during the later course of the hospital stay in a further 11 patients (9.8%). The mean survival time was 13.7 +/- 17.7 months. Over the entire observation period of 23 +/- 21 months, 67 patients died (59.8%); the cause of death was hemorrhage in 4.5%, the underlying hepatic disease in 65.7%, and non-hepatic causes in 29.8%. Recurrent bleeding occurred in 58 patients (51.7%). The cumulative survival rate in the patients treated with cyanoacrylate and polidocanol was 66 +/- 15% and 26 +/- 32% after one and five years, respectively, and 56 +/- 13% and 33 +/- 19% in those treated with polidocanol alone. CONCLUSIONS: Endoscopic treatment of esophageal varices with cyanoacrylate and polidocanol, or polidocanol alone, is effective in controlling bleeding, and the complication rate is tolerable. The short-term and long-term mortality rates are determined largely by the underlying liver disease.

[Diseases of the esophagus in the elderly. Deglutition disorders--intermittent thoracic pain--retrosternal burning pain]. / Erkrankungen des Osophagus im Alter. Schluckstörungen--intermittierende Thoraxschmerzen--retrosternales Brennen.

As a contribution to the polymorbidity of geriatric patients, gastrointestinal diseases are numerically of only minor importance, occurring four to five times less frequently than diseases of the cardiovascular system. However, a number of gastrointestinal diseases are more commonly found in the elderly than in the younger patient. The symptoms of esophageal diseases include dysphagia, odynophagia, pyrosis, and intermittent chest pain. New developments in the area of drug treatment, and minimally invasive endoscopic procedures usually now permit age adaptet therapeutic management to be offered.

[Reflux esophagitis--diagnosis and differential diagnosis]. / Refluxösophagitis--Diagnose und Differentialdiagnose.

The combination of the two typical symptoms - heartburn and regurgitation - is almost proving gastrooesophageal reflux disease (GORD). Further - atypical - symptoms are dysphagia, odynophagia, pharyngitis, reflux-induced pulmonary symptoms or intermittent chest-pain. Endoscopic signs of GORD are patchy reddening of the mucosa, erosions, ulcers and stricture. Barretts oesophagus is characterized by columnar epithelial metaplasia. Consequence: Typical symptoms of GORD may be treated without further diagnostic procedure whereas in the case of atypical symptoms diagnosis of GORD has to be established by endoscopy.

[Gastroenterology in Germany--determination of current status and perspectives. Results of a survey among members of the German Society of Digestive and Metabolic Diseases]. / Gastroenterologie in Deutschland--Standortbestimmung und Perspektiven. Ergebnisse einer Umfrage unter Mitgliedern der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.

UNLABELLED: The present survey carried out among the members of the German Society of Gastroenterology and Metabolism (GSGM) was intended 1. to provide information on a) age, professional experience and nature of present activities, b) the service spectrum, c) career prospects, and 2 to reflect the views of those questioned on a) the ability of non-gastroenterologists to furnish gastroenterological services, b) the performance of invasive procedures on an ambulatory basis, c) requirements to be met by gastroenterological training, d) quality assurance measures, and e) the public image of the specialty gastroenterology. METHOD: A questionnaire was sent to the members of the GSGM, of whom 629 responded and whose questionnaires were evaluated. RESULTS: The median age of the responders was 48,2 years, median duration of professional activity was 15 years; 73% work in a hospital setting. Some 76-88% of those working in hospitals consider their future activities to be in the hospitals. Provided that strict, in part yet to be defined, specialty-related conditions are met, gastroenterological services can also be provided by non-gastroenterologists. Some 50% of the responders were against the performance of invasive endoscopic procedures on an ambulatory basis (e.g. EPT, lithotripsy, stent implantation). In the opinion of the majority, the number of doctors undergoing specialist training with the aim of becoming qualified gastroenterologists should not be limited. The majority of responders were also in favour of quality assurance measures as well as clinical research in this area. Almost three-quarters of the responding members of the GSGM perceived shortcomings in the public image of gastroenterology. CONCLUSION: The analysis of the results of the present survey indicate prospects for the future, but also a need for action in the field of the specialty gastroenterology.

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.

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.

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.

Comparison of pancreatic morphology and exocrine functional impairment in patients with chronic pancreatitis.

A comparative analysis of pancreatic morphology and exocrine function was performed prospectively in 48 patients. All patients had transabdominal ultrasound, computed tomography, endoscopic retrograde pancreatography, and a secretin-caerulein test. Classification of ultrasound, computed tomography, and pancreatogram findings was based on the Cambridge classification. In 10 patients, no pancreatic duct changes were detected on pancreatography. Equivocal (Cambridge I), mild to moderate (Cambridge II), and considerable ductal changes (Cambridge III) were found in 10, 12, and 16 patients, respectively. Computed tomography and ultrasound changes were found to correlate in 40-50%, 67%, and 94-100% of patients with Cambridge I, II, and III abnormal duct morphology, respectively. In patients with a normal pancreatogram, no patient had a functional impairment. Seventy per cent of the patients with equivocal pancreatic duct changes had dissociated, and 30% global, pancreatic insufficiency, while 50% of those with mild to moderate abnormal duct morphology manifested dissociated, and 50% global, functional impairment. All patients with considerable pancreatic duct changes had global pancreatic insufficiency. The results of this study confirm that normal endoscopic retrograde pancreatographic findings and Cambridge III ductal changes on endoscopic retrograde pancreatography correlate extremely well with normal pancreatic function and advanced functional insufficiency, respectively. As diagnostic tools, ultrasound and computed tomography are as sensitive as pancreatography only in chronic pancreatitis with considerable morphological changes.

[Gastroesophageal reflux. Pathophysiology, diagnosis and rational therapy]. / Gastroösophageale Refluxkrankheit. Pathophysiologie, Diagnostik und rationelle Therapie.

A combination of the typical symptoms heartburn and regurgitation may be considered virtual proof of gastroesophageal reflux disease. In the case of the atypical symptoms dysphagia, odynophagia, pharingitis, reflux-induced attacks of respiratory distress and intermittent chest pain further diagnostic investigation is indicated. Endoscopy reveals patchy reddening and possibly erosions, ulcers and strictures. Although the decisive pathophysiological factor in reflux disease is motility, the use in particular of acid suppressors represents an important part of treatment; in more severe reflux esophagitis (grades III and IV), proton pump inhibitors are the drugs of first choice. Gastro-esophageal reflux disease is a chronic condition with a recurrence rate of 60-80 percent. For prophylaxis, the minimum dose of antacids required to treat the stage must be administered.