The Role of Potassium Channels in Relaxant Effect of Levosimendan in Rat Small Mesenteric Arteries

Summary We investigated both the effect of levosimendan and the role of various potassium channels in KCl-precontracted rat small mesenteric arteries. Levosimendan (10⁻⁶−10⁻³ M) or cromakalim (CRO, 10⁻⁷−10⁻⁴ M) produced concentration-dependent relaxation responses in small mesenteric arteries precontracted by 30 mM KCl. The relaxant responses to levosimendan in KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of rat small mesenteric arterial segments with ATP-dependent potassium channel (KATP) blocker glibenclamide (GLI, 10⁻⁶ M) for 30 min significantly inhibited the relaxant responses to both levosimendan and CRO. Neither the Ca²⁺-activated potassium channel (KCa) blocker iberiotoxin (10⁻⁷ M) nor the voltage-dependent potassium channel (KV) blocker 4-aminopyridine (5 mM) incubation for 30 min caused significant alterations in relaxant responses to levosimendan in KCl-precontracted small mesenteric arteries. These findings suggested that levosimendan-induced relaxation responses in isolated rat small mesenteric arteries were neither depended on endothelium nor inhibited by the blockers of KV or KCa but, they rather seem to depend on the activation of KATP.     

Effects of formaldehyde inhalation on the junctional proteins of nasal respiratory mucosa of rats

Exposure to formaldehyde, which is an organic compound, disturbs the integrity of nasal mucosa. In this study, we aimed to clarify the protein changes in the junctional complex of nasal mucosa of Wistar rats exposed to formaldehyde inhalation.The study was performed in 20 female Wistar rats. Rats were divided into two groups randomly. Control rats were allowed free access to standard rat chaw and tap water (n:10). Experimental group was exposed to formaldehyde vapor at 15 ppm, 6 h/day, 5 days/week for 12 weeks (n:10). Histological evaluation of the experimental model was determined by hematoxylin-eosin (HE) and periodic acid Schiff (PAS) stainings of paraffin-embedded nasal mucosa tissues and by electron microscopy. The effects of formaldehyde inhalation on the distribution of occludin, E-cadherin, and γ-catenin were assessed by immunohistochemistry.The nasal mucosa of the experimental group was correlated with hypertrophy in goblet cell, degeneration in basal lamina, stratification of epithelium, and proliferation. Thickness of basal lamina and also local degenerative regions, vacuole increase in cytoplasmic areas, irregular forms of kinocilium and loss of sharpness in the kinocilium membrane were the findings at the ultrastructural level. The expressions of E-cadherin, occludin, γ-catenin proteins in intercellular junctional complexes of rat nasal mucosa were also decreased in experimental group compared to control group.The findings of the present study indicated that formaldehyde vapor inhalation in the concentrations and duration of exposure used in the present experiment significantly decreased the density of structural proteins of the junctional complex in the nasoepithelium. It was suggested that, the formaldehyde inhalation could cause complete impairment of intercellular junctional complexes and disturb the tissue integrity in nasal mucosa at higher concentrations.     

Transplantation of bioreactor-produced neural stem cells into the rodent brain

The development of new cell replacement strategies using neural stem cells (NSC) may provide an alternative and unlimited cell source for clinical neural transplantation in neurodegenerative diseases such as Parkinson's and Huntington's disease. The clinical application of neural transplantation using NSC will therefore depend upon the availability of clinical grade NSC that are generated in unlimited quantities in a standardized manner. In order to investigate the utility of NSC in clinical neural transplantation, undifferentiated murine NSC were first expanded for an extended period of time in suspension bioreactors containing a serum-free medium. Following expansion in suspension bioreactors, NSC were still able to differentiate in vitro into both astrocytes and neurons after exposure to brain-derived neurotrophic factor (BDNF), suggesting that bioreactor expansion does not alter cell lineage potentiality. Undifferentiated bioreactor-expanded NSC were then transplanted into the rodent striatum. Immunohistochemical examination revealed undifferentiated bioreactor-expanded NSC survived transplantation for up to 8 weeks and expressed the astrocytic immunohistochemical marker glial fibrillary acidic protein (GFAP), suggesting that the host striatal environment influences NSC cell fate upon transplantation. Moreover, no tumor formation was observed within the graft site, indicating that NSC expanded in suspension bioreactors for an extended period of time are a safe source of tissue for transplantation. Future studies should focus on predifferentiating NSC towards specific neuronal phenotypes prior to transplantation in order to restore behavioral function in rodent models of neurodegenerative disease.     

Unrecognized side effect of statin treatment: unilateral blepharoptosis

A 43-year-old man receiving statin monotherapy (10 mg atorvastatin) for hypercholesterolemia had unilateral blepharoptosis as the result of isolated myositis of the levator muscle. Statin-induced myositis in the levator muscle should be considered in the differential diagnosis of acquired unilateral blepharoptosis of unknown cause.     

Comparision of the inotropic effects of levosimendan, rolipram, and dobutamine on human atrial trabeculae

The aim of this study was to compare the positive inotropic effects of 3 different agents with 3 different mechanisms of actions-levosimendan, rolipram, and dobutamine-on human atrial trabecular muscles. Samples of right atrial appendage (1 cm, 500-1000 mg) were removed and immersed in preoxygenated and modified Tyrode solution. In oxygenated Tyrode solution, preparations were used to investigate the concentration-effect relationship of levosimendan, dobutamine, and rolipram on percentage developed tension (DT), from 10 to 10 M, each concentration for 15 minutes. All 3 agents produced concentration-dependent increments in DT. We found that levosimendan was the most efficacious positive inotropic agent on isolated human atrial trabeculae. Both the sensitivity (pD2) and maximum response (Emax) of human atrial trabeculae to levosimendan (6.711 +/- 0.26 and 23.2 +/- 2.2 mN, respectively) were significantly greater than those of dobutamine (6.663 +/- 0.19 and 17.6 +/- 2.8 mN) and rolipram (6.497 +/- 0.18 and 15.0 +/- 1.0 mN). pD2 and Emax values for dobutamine were significantly higher than those for rolipram. It was suggested that because of its potential to enhance cardiac performance without predisposition to calcium-induced arrhythmias, levosimendan might be more useful as a positive inotropic agent in clinical practice.     

Comparison of chest radiography and high-resolution computed tomography findings in early and low-grade coal worker's pneumoconiosis

INTRODUCTION: High-resolution computed tomography (HRCT) is more sensitive than chest X-ray (CXR) in the depiction of parenchymal abnormalities. We aimed to present and compare CXR and HRCT findings in coal workers with and without early and low-grade coal worker's pneumoconiosis (CWP). MATERIALS AND METHODS: 71 coal workers were enrolled in this study. All workers were male. The CXR and HRCT of those workers were obtained and graded by two trained readers. HRCT's were graded according to Hosoda and Shida's Japanese classification. After grading, 67 workers with CXR profusion 0/0-2/2 were included in the study. Four patients with major opacity were excluded. Profusion 0/1 to 1/1 cases were accepted as early and profusion 1/2 and 2/2 cases as low-grade pneumoconiosis. RESULTS: Discordance between CXR and HRCT was high. Discordance rate was found higher in the early pneumoconiosis cases with negative CXR than low-grade pneumoconiosis (60, 36 and 8%, respectively). When coal miners with normal CXR were evaluated by HRCT, six out of 10 cases were diagnosed as positive. In low-grade pneumoconiosis group, the number of patients with positive CXR but negative HRCT were low in comparison to patients with CXR negative and early pneumoconiosis findings. Most of the CXR category 0 patients (10/16) were diagnosed as category 1 by HRCT. Eleven cases diagnosed as CXR category 1 were diagnosed as category 0 (7/11) and category 2 (4/11) by HRCT. In CXR category 2 (eight cases), there were four cases diagnosed as category 1 by HRCT. CONCLUSIONS: Discordance between CXR and HRCT was high, especially for CXR negative and early pneumoconiosis cases. The role of CXR in screening coal workers to detect early pneumoconiosis findings should be questioned. We suggest using HRCT as a standard screening method instead of CXR to distinguish between normal and early pneumoconiosis.     

MR imaging features of foot involvement in ankylosing spondylitis

OBJECTIVE: To determine alterations of the soft tissue, tendon, cartilage, joint space, and bone of the foot using magnetic resonance (MR) imaging in ankylosing spondylitis (AS) patients. MATERIALS AND METHOD: Clinical and MR examination of the foot was performed in 23 AS patients (46 feet). Ten asymptomatic volunteers (20 feet) were studied on MR imaging, as a control group. MR imaging protocol included; T1-weighted spin-echo, T2-weighted fast-field echo (FFE) and fat-suppressed short tau inversion recovery (STIR) sequences in sagittal, sagittal oblique, and coronal planes using a head coil. Specifically, we examined: bone erosions, tendinitis (acute and chronic), para-articular enthesophyte, joint effusion, plantar fasciitis, joint space narrowing, soft tissue edema, bone marrow edema, enthesopathy in the Achilles tendon and plantar fascia attachment, subchondral signal intensity abnormalities (edema and sclerosis), tenosynovitis, retrocalcaneal bursitis, subchondral cysts, subchondral fissures, and bony ankylosis. Midfoot, hindfoot, and ankle were included in examined anatomic regions. RESULTS: Clinical signs and symptoms (pain and swelling) due to foot involvement were present in 3 (13%) of the patients while frequency of involvement was 21 (91%) with MR imaging assessment. The MR imaging findings were bone erosions (65%), Achilles tendinitis (acute and chronic) (61%), para-articular enthesophyte (48%), joint effusion (43%), plantar fasciitis (40%), joint space narrowing (40%), subchondral sclerosis (35%), soft tissue edema (30%), bone marrow edema (30%), enthesopathy of the Achilles attachment (30%), subchondral edema (26%), enthesopathy in the plantar fascia attachment (22%), retrocalcaneal bursitis (22%), subchondral cysts (17%), subchondral fissures (17%), tendinitis and enthesopathy of the plantar ligament (13%), and bony ankylosis (9%). The most common involved anatomical region was the hindfoot (83%) following by midfoot (69% ) and ankle (22%). CONCLUSION: In our experience, MR imaging may detect inflammatory and/or erosive bone, soft tissue, cartilage, tendon, and joint abnormalities in AS patients, even if AS patients did not have clinical signs and symptoms of foot involvement. If these data prove to be confirmed in further MR studies, MR imaging may be of importance especially in early diagnosis of inflammatory changes in the foot.     

One-stage operation for hydatid disease of lung and liver: principles of treatment

OBJECTIVE: Hydatid disease is endemic in many countries throughout the world. Although we do not have exact figures, the disease is prevalent in Turkey. A considerable number of patients have additional liver cysts as well. In this study we reviewed our experience with hydatid disease of the lung and liver and discussed the principles of treatment. METHODS: From 1971 to 1999, 2509 patients with pulmonary hydatidosis were referred to us, and 485 of them had concomitant liver cysts. Of these, 405 patients had cysts located on the dome of the liver, and they were operated on with phrenotomy through a right thoracotomy. Eighty patients who were found to have concomitant liver cysts in the lower part of the liver were referred to general surgery for a laparotomy. RESULTS: Hydatid cysts located in the lungs were managed by means of cystotomy and capitonnage. For liver cysts, cystotomy and inversion of the cavity with sutures was the surgical method of choice, and a drain was left in place. In case of multiple cysts in the liver, needle aspiration was preferred. Twelve major complications, including excessive biliary drainage and bronchobiliary fistula, occurred in these patients. CONCLUSIONS: We believe that management of pulmonary and hepatic cysts simultaneously through the thoracic route is convenient and should be encouraged in patients because this prevents a second operation. Needle aspiration can be applied only for liver cysts. It is absolutely contraindicated in lung hydatid cysts.     

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus

BACKGROUND: The successful excision of a renal cell carcinoma (RCC) invading the inferior vena cava (IVC) remains a technical intraoperative challenge and requires a careful preoperative surgical management planning. Although a radical operation remains the mainstay of the therapy for RCC, the optimal management of the patients with RCC causing IVC tumor thrombus remains unresolved. In this study, we reviewed our experience in this group of patients and herein report the results. METHODS: Between July 1990 and August 1998, 11 patients with RCC with IVC tumor thrombus underwent surgical treatment. The mean patient age was 54.2 years and the male to female ratio was 1.75. The cephalad extension of the tumor was suprarenal in all cases, being infrahepatic in 6 patients, intrahepatic in 2, and suprahepatic with right atrial extension in 3 patients. All tumors were resected via inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of vena cavotomy. Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) were used in 3 patients. RESULTS: The mortality rate was 9.1% (1 patient was lost on the 11th postoperative day). Complications occurred in 3 patients. The remaining 10 patients (90.9%) could be successfully discharged from hospital. Two of them were lost during follow-up because of tumor progression at the 43rd and 54th postoperative months. The 10-year Kaplan-Meier survival estimate was 71.4%, with a mean follow-up of 4.6 years. The presence of lymph node metastases and perinephric spread seemed to possess an adverse effect on the survival. Although the groups included small numbers of patients, there was no significant difference in survival in regard to the different levels of tumor thrombus extension into the vena cava. CONCLUSIONS: Surgical treatment is the preferred approach to patients with RCC and IVC tumor thrombi as it provides markedly better results when compared with the other therapeutical modalities. We believe that complete surgical excision of the tumor and the resulting thrombus with appropriate preoperative staging and a well-planned surgical approach, using CPB and DHCA when necessary, provide an acceptable long-term survival with a good quality of life expectation.