Lipopolysaccharide-induced lung inflammation is inhibited by neutralization of GM-CSF

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the pathogenesis of acute and chronic lung disease as a major regulator governing the functions of granulocyte and macrophage lineage populations. Chronic obstructive pulmonary disease (COPD) is a disease characterized by lung inflammation with accumulation of neutrophils and increased levels of pro-inflammatory cytokines including GM-CSF in the patient's lungs. We used intranasal administration of lipopolysaccharide (LPS) to mice to induce a disease that resembles COPD with pulmonary inflammation, neutrophil recruitment and release of pro-inflammatory mediators in the bronchoalveolar lavage fluid of the diseased mice. 2 h prior to LPS administration, mice were systemically treated with the murine GM-CSF neutralizing antibody mAb 22E9 per intraperitoneal injection. Intranasal challenge with LPS-induced an increase of total cell number and of neutrophils in the bronchoalveolar lavage fluid. Elevated levels of tumor necrosis factor alpha (TNF-alpha), keratinocyte cytokine and macrophage inflammatory protein-2 (MIP-2) were also observed at this time point. GM-CSF was no longer detectable in bronchoalveolar lavage fluid at 24 h due to its early expression with a peak reached 6 h after LPS challenge. Pretreatment of mice with GM-CSF neutralizing antibody dose-dependently inhibited the accumulation of neutrophils and reduced TNF-alpha and MIP-2 protein levels in bronchoalveolar lavage fluid. These data suggest that neutralization of GM-CSF may represent a novel treatment modality for lung inflammation and in particular for COPD.     

Cervical lymphodenopathy--a single presentation of sarcoidosis?

BACKGROUND: Sarcoidosis is a chronic inflammatory disease, commonly found in lungs and hilar lymph nodes, but multiple organs could be involved. The diagnosis is based on specific pathohistology which should be always combined with clinical, radiological and laboratory findings. CASE REPORT: A patient initially presented with pneumonia, and treated with antibiotics, but with the general symptoms that persisted despite radiological resolution of lung infiltration was reported. The further diagnostic procedures revealed the presence of sarcoid granulomas in cervical lymph nodes. The peripheral lymph nodes are often affected in the early course of the disease, but it is difficult to distinguish if the illness is a sarcoid reaction to lung infection or a acute onset of sarcoidosis. CONCLUSION: The detection of sarcoid granulomas in cervical lymph nodes should be precisely analyzed for the presence of sarcoidal changes in other tissues, primarily in the lungs tissue. Early diagnosis of lung sarcoidosis is significant, especially in the light of the fact that the latest studies point out that the prednisone therapy, started immediately after the diagnosis has been made, renders positive effects also in asympthomatic patients in II and III phase of the disease.     

Proinflammatory cytokines (IL-1β and TNF-α) and chemokines (IL-8 and MIP-1α) as markers of peri-implant tissue condition

Analysis of peri-implant crevicular fluid (PICF) offers a non-invasive means of studying the host response in peri-implant disease and may provide an early indication of patients at risk for active disease. This study examined the PICF levels of interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α), interleukin-8 (IL-8) and macrophage inflammatory protein-1alpha (MIP-1α) in patients with non-manifesting inflammation, early and late stages of mucositis. The study group comprised 90 adult healthy volunteers with endosseal titanium implants inserted. Samples were taken from peri-implant sulcus using a filter paper technique. Implant tissues were categorized clinically as healthy, early mucositis or advanced mucositis. Clinical manifestations were determined by: gingival index and bleeding on probing, plaque index and radiographic analyses. Cytokine concentrations were assesed using commercially available enzyme-linked immunosorbent assay kits. Patients from the control group (healthy patients) have significantly lower concentrations of IL-1β, TNF-α, IL-8 and MIP-1α in PICF compared with both groups with mucositis. Positive correlation was noted in the control group between IL-1β and TNF-α and between MIP-1α and IL-8 in the group with early mucositis. The results suggest that cytokines could be prognostic markers of implant failure.     

Single-dose intravenous simvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in the rat

The effect of acute pretreatment with a single dose of simvastatin (1 mg/kg, i.v.; 30 min before ischemia) on renal dysfunction caused by ischemia-reperfusion (I/R) injury in the rat was investigated. I/R injury was induced by clamping both renal vascular pedicles for 45 min, followed by 4 h of reperfusion with saline (2 ml/kg per hour). Simvastatin significantly improved both parameters of glomerular and tubular dysfunction (e.g., creatinine levels and fractional excretion of Na(+), respectively) and especially improved the histological score, compared to control I/R-injured rats treated with saline or 10% DMSO only.     

Neuroendocrine tumor of the skin of head and neck

BACKGROUND: Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. CASE REPORT: We showed two cases (females of 89 and 70 years old) hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the begining of the treatment. The second patient with this neuroendocrine tumor with the high malignacy potential and huge regional metastasis, was treated surgiclly, and died a month and a half after the operation. CONCLUSION: These two cases confirmed the aggressive and recidivant growth of this tumor with the difficut pathologic investigetion, and the extremlly bad prognosis inspite of the treatment.     

A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy

STUDY OBJECTIVES: To measure the effect of nocturnal sodium oxybate administration on sleep architecture in patients with narcolepsy. DESIGN: Open-label study. SETTING: Four accredited sleep clinics. PARTICIPANTS: 25 adult patients with narcolepsy-cataplexy. INTERVENTIONS: Patients were weaned from previously used anticataplectic medications and administered increasing nightly doses of sodium oxybate over a 10-week period: 4.5 g for 4 weeks, 6 g for 2 weeks, 7.5 g for 2 weeks, and 9 g for 2 weeks. The effect of sodium oxybate was measured using nocturnal polysomnograms, the Epworth Sleepiness Scale, the Maintenance of Wakefulness Test, and a narcolepsy symptoms questionnaire. RESULTS: The nightly administration of sodium oxybate produced dose-related increases in slow-wave sleep and delta power, rapid eye movement sleep increased initially and then decreased in a dose-related manner, nocturnal awakenings decreased, and daytime sleep latency increased. Significant improvements in daytime symptoms were measured by the Maintenance of Wakefulness Test, the Epworth Sleepiness Scale, and the narcolepsy symptom questionnaire. CONCLUSIONS: Nocturnal administration of sodium oxybate in patients with narcolepsy produces significant improvements in sleep architecture, which coincide with significant improvements in daytime functioning.     

Familial adenomatous polyposis with extracolonic manifestations--case report

The familial adenomatous polyposis syndrome is an autosomal dominant inherited disease characterized by progressive development of multiple adenomatous polyps throughout the colon and rectum. Due to the malignant potential of adenomatous polyps, colorectal cancer develops in 100% of cases, approximately 10-15 years after the onset of symptoms. Extracolonic manifestations of the disease including adenomatous polyps of the stomach, duodenum, small intestine and periampullatory region are rare. The etiology of the disease is germline mutation at the site of tumor suppressor gene located on chromosomes 5q21-22. A case is described of a 48-year-old man hospitalized at the Department of Abdominal Surgery, Sveti Duh General Hospital in Zagreb for the treatment of familial adenomatous polyposis syndrome. For some time the patient reported occasional abdominal pain, frequent stools and diarrhea with blood, anemia and body weight loss. Laboratory, radiology and endoscopy examinations verified multiple adenomatous polyps of the colon and rectum, also with polyps of the stomach, duodenum and jejunum. Histopathology confirmed the polyps to show moderately poorly differentiated cylindric epithelium and moderate to severe dysplasia. Radical surgery was required, so proctocolectomy with Brook ileostomy was performed. The postoperative recovery and wound healing were normal. The patient was discharged twelve days of the surgery for home care. Oncologic treatment was suggested. Verified extracolonic manifestations of the disease require periodical endoscopic follow up and possible treatment.     

Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.     

Mercury chloride genotoxicity in rats following oral exposure, evaluated by comet assay and micronucleus test

Mercury is a toxic element which is easily absorbed after ingestion or inhalation and deposited mainly in the kidney. The aim of this study was to evaluate the effects of mercury chloride in rats. Female rats, aged 14 weeks, were receiving mercury chloride in oral doses of 0.068, 0.136, and 0.272 mg kg(-1) body weight (b.wt.) for five consecutive days. Three days after the last dose, the animals were killed. The liver and the kidney were dissected and mercury measured using vapour generation atomic absorption spectrometry. The results show a significant increase in mercury mass fraction in the kidney after two higher doses of mercury chloride, while liver mercury burden showed a significant increase only after the highest dose. Blood samples were analysed using the comet assay and supravitally acridine orange stained micronucleus test. Tail length, tail moment and micronucleus frequency were significantly higher in the treated rats than in control rats, regardless of the dose of mercury chloride, while the difference between the treated groups for both comet and micronucleus parameters was not statistically significant.