Experimental investigation of the efficiency of antibiotics in the critical size bone defects following radiotherapy

Amaç: Çenelerin osteoradyonekrozu (ORN), baş ve boyun kanserlerinde radyasyon tedavisinin bir komplikasyonu olarak karşımıza çıkmaktadır. Tanımı ve sınıflandırması yıllar içinde değişiklik göstermiş, patofizyolojisine dair teorileri geliştirilmiş ve buna bağlı olarak farklı tedavi prensipleri denenmiştir. Çalışmadaki amacımız, radyoterapiyi takiben alt çene kemiğinde cerrahi olarak oluşturulan kritik boyuttaki defektlerde klindamisin, metronidazol, rifamisin ve doksisiklin grubu antibiyotiklerin kemik iyileşmesi üzerindeki etkilerini incelemektir. Gereç ve Yöntem: Anti-enflamatuar etkinliğin kemik iyileşmesi üzerindeki etkilerini değerlendirmek için, 50 adet Wistar cinsi albino türü sıçanlar kullanılmıştır. Tüm gruplara genel anestezi altında 30 Gy dozda radyoterapi uygulandıktan 8 hafta sonra sıçanların sağ mandibulasında 5 mm çapında bikortikal hazırlanan kemik defektlerine deney gruplarında ksenogreft ile karıştırılan antibiyotikler, kontrol gruplarında ise sadece ksenogreft partikülleri uygulanarak cerrahi saha iyileşmeye bırakılmıştır. Sakrifikasyon sonrasında elde edilen örneklerde enflamasyon, nekroz, fibrozis, yeni kemik yapım alanı, kalsifiye olmuş kemik alanı ve kapiller sayısı histopatolojik ve histomorfometrik olarak değerlendirilmiştir. Bulgular: İncelenen kesitlerde nekroz, enfeksiyon ya da fibrozis bulgusuna rastlanmamıştır. Kontrol grubu ile yapılan karşılaştırmalarda metronidazol ve klindamisin gruplarında yeni kemik yapım alanlarının anlamlı derecede yüksek olduğu görülmüştür (p<0.01, p<0.01). Kalsifiye kemik trabekül alanları incelendiğinde kontrol grubu ile klindamisin grubu arasında istatistiksel olarak ileri derecede anlamlı fark tespit edilmiştir (p<0.01). Klindamisin ile diğer gruplar karşılaştırıldığında ise aradaki fark anlamlı (p<0.05) bulunmuştur. Kontrol grubu ile yapılan karşılaştırmalarda kapiller sayısı metronidazol grubunda anlamlı (p<0.05), klindamisin grubunda (p<0.01) ise ileri derecede anlamlı olarak farklı bulunmuştur. Sonuç: Antibiyotik uygulanan gruplarda iltihabi alanların sayısında azalma, yeni kemik yapım alanlarında ve damarlanmada artış gözlenmiştir. Çalışmada kullandığımız antibiyotiklerin antibakteriyel aktiviteden bağımsız olarak anti-enflamatuar etkinliklerinin olabileceği düşünülmektedir.Background: Osteoradionecrosis of the jaws is a complication of radiation treatment for cancer of the head and neck. Its definition and classification have changed over the years and theories of its pathophysiology have evolved and led to new treatments. This study aimed to investigate the effects of clindamycin, metronidazole, rifamycin and doxycycline on bone healing in the surgically created critical size defects in the bone of lower jaw, following radiotherapy. Methods: To investigate the effect of anti-inflammatory function on bone healing, 50 Wistar albino rats were used. Following radiotherapy, bicortical bony defects in 5 mm diameter was created in the right mandible of every rats, filled with antibiotics and xenograft in the experimental groups, and with only xenograft particles in the control groups. After sacrification period, all specimens were evaluated in terms of inflammation, necrosis, fibrosis, new bone formation areas, calcified trabecular bone areas and capillary count, histologically and histomorphometrically. Results: None of the specimens showed symptoms of necrosis, infection or fibrosis. The new bone formation areas were significantly higher in metronidazole and clindamycin groups when compared with control group (p<0.01, p<0.01). As the calcified bone trabecular areas were examined, there was a statistically significant difference between the control and clindamycin group (p <0.01). As the group of clindamycin was compared with other groups, the difference was also statistically significant (p<0.05). The capillary count was significantly different in the groups of metronidazole (p<0.05) and clindamycin when compared with the control group (p<0.01). Conclusion: Inflammatory reaction decreased in the groups treated with antibiotics, the areas of new bone formation and capillarity increased. Based on this study results, antibiotics might have anti- inflammatory activities independent of their antibacterial properties

Effects of losartan on the renin-angiotensin-aldosterone system and erythrocytosis in patients with chronic obstructive pulmonary disease and systemic hypertension

WOS: 000168891200003Objective: To evaluate the effects of losartan on blood pressure, erythrocytosis and the renin-angiotensin-aldosterone system (RAS) in patients with erythrocytosis and hypertensive chronic obstructive pulmonary disease (COPD). Design: Prospective, nonrandomised, two-period study. Patients and Participants: 24 patients were recruited, of whom 20 (17 men) completed the trial. The mean age was 55 +/- 8 years (range 40 to 65 years). Erythrocytosis was defined as a persistent elevation of the haematocrit to greater than or equal to 47% in females and greater than or equal to 50% in males. Patients were less than or equal to 65 years of age and hypertensive according to the WHO criteria. Patients who had hepatic and/or renal dysfunction, acute exacerbation of primary disease, were taking systemic corticosteroids, had any other systemic disease, or showed intolerance during the washout period were excluded. Methods: An initial 2-month period on, a standard regimen with nasal oxygen (2 L/min, 18 h/day) and bronchodilators (inhaled salbutamol, oral theophylline, inhaled ipratropium bromide) was followed by a second 2-month period during which losartan was administered as an antihypertensive agent in addition to standard therapy. Routine biochemical and haematological monitoring was carried out. Systolic and diastolic blood pressures (SBP and DBP respectively) were measured. ECG and arterial blood gas analyses were also performed for all patients at the beginning of the study, and all of these clinical and laboratory investigations were performed at 15-day intervals during the study. Plasma renin activity and serum aldosterone and erythropoietin levels were measured both at the beginning and at the end of each 2-month period. Results: No statistically significant changes were found in the measured parameters at the end of the 2-month standard treatment period. Fatigue and dizziness were reported by four of the patients during the first week of losartan treatment. Both SEP and DBP decreased by 10mm Hg with losartan treatment (p = 0.0003 and 0.0002, respectively). Haematocrit decreased from 53 +/- 3% to 48 +/- 4% (p = 0.0001). The mean arterial blood gas tension of CO2 (pCO(2)) was 54 +/- 11mm Hg and decreased to 48 +/- 4mm Hg (p = 0.01). Losartan treatment decreased serum aldosterone to 259 +/- 148 ng/dl from a mean baseline value of 156 +/- 140 ng/dl (p = 0.03). There were no statistically significant changes in pO(2) serum erythropoietin or plasma renin activity. Conclusion: Losartan controls blood pressure and reduces erythrocytosis in patients with hypertensive COPD, and is well tolerated. Although the mechanism of the effect of losartan on erythrocytosis requires further investigation, we propose that the RAS, in particular angiotensin II, has effects on the haemopoietic system and that blocking these effects decreases the haematocrit