Oral toxicity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin: comparison of biomechanical and histopathological effects on Achilles tendon in rats

Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p<0.05 and p<0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.     

Increased soluble glycoprotein V concentration during the acute onset of unstable angina pectoris in association with chronic cigarette smoking

Platelet hyperactivity is important in the pathobiology of acute coronary syndromes. Glycoprotein V (GPV) is an integral membrane protein of platelets in the function of the GPIb-V-IX receptor for vWf/shear-dependent platelet adhesion in arteries. Soluble GPV is a novel marker of platelet activation. The aim of this study is to assess circulating soluble GPV levels in unstable angina pectoris (UA). Twenty-one patients (15 men, six women, aged 52?±?7 years) with UA pectoris were studied. The inclusion criteria were angina at rest lasting >20?min during the preceding 6?h, with transient ST segment depression and/or T wave inversion and no evidence of myocardial infarction detected with the use of cardiac troponin-T. Coronary artery stenosis was angiographically confirmed in all patients. Twenty age- and sex-matched healthy adults (14 men, six women, aged 48?±?7 years) served as controls. There were no significant differences among the studied groups with respect to age, sex, obesity, smoking, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and platelet counts. Plasma-soluble GPV concentrations were higher in the UA patient group (126?±?46?ng/ml) than those in the healthy controls (82?±?15?ng/ml) (P?=?0.001). There was a significant correlation only between plasma-soluble GPV levels and smoking (r?=?0.526, P?=?0.0001). Smoker UA patients had higher levels of soluble GPV than the non-smoker patients (139?±?40 vs. 113?±?50?ng/ml, respectively, P?=?0.02). However, soluble GPV levels were similar in smoker and non-smoker healthy controls (P?=?0.2). It is concluded that soluble GPV concentrations are significantly increased during the acute clinical course of unstable angina pectoris, indicating that soluble GPV may be useful marker of platelet activation in those patients. The level of the molecule is significantly affected from smoking in those patients.     

Scintigraphic imaging of infections with 99m-Tc-labelled glutathione liposomes

In this study, liposomes containing glutathione were evaluated to detect infection in mice. Glutathione liposomes were labelled by using 99mTclabelled-HMPAO (hexamethyl propylamine oxime). Mice were infected in the thigh by intramuscular injection with turbentine. Labelled liposomes were applied to the tail vein of the mice intravenously. At fixed time intervals they were sacrificed. The animals were imaged under a gamma camera. Then, tissue samples were excised and radioactivity of all organs was counted. Abscess-tomuscle, abscess-to-liver, and abscess-to-spleen ratios were calculated. The ratios of abscess-to-muscle were found to be 1.6 and 11.6 at 1h and 24h, respectively. According to these data, the abscess can be defined at 1h and it became more clear with time.     

Evaluation of 99mTc labelled poly lactic acid microspheres for diagnostic radioembolization

Radioembolization is used in diagnostic imaging of the lungs and for radioembolization therapy of hepatic tumours. Presently, 99mTc labelled macroaggregates or microspheres of human serum albumin (HAM) are used for this purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is not a blood product. The aim of the present study was to evaluate the uptake and biodegradation of PLA microspheres in lungs. PLA (MW=48720Da) microspheres of 1.0-100mum (mean=39.5mum) in diameter were prepared by solvent evaporation frommethylene chloride. They were labelled with 99mTcby stannous chloride reduction at pH3, with an efficiency of 98%and a stability of 96%at 24h. For biodistribution studies, 15 mice were i.v. injected with 20muCi 99mTc-PLA microspheres in 0.1ml and sacrified at 15min, 1, 3, 6 and 24h (three at each time point). All the organs were removed, weighed and counted against a standard prepared from 1/100 dilution of the injected radioactivity. Some mice were similarly injected and sacrified at 30min, 15 and 30 days. The lungs were removed and frozen, and 10mum sections were obtained, stained with haemotoxylin and eosin and examined under a light microscope. Five rabbits were i.v. injected with 1mCi of 99mTc-PLA microspheres. Scintigrams were obtained at various intervals up to 24h. In mice, the lung uptake was significant at 30min-1h post-injection. In rabbits, the lungs were the only organs visualized up to 24h. Microscopic examination of tissue sections demonstrated slow biodegradation of PLA particles. In conclusion; (1) The high lung uptake obtained in mice and rabbits indicates the suitability of PLA microspheres for lung imaging, and (2) although the slow biodegradation rate might be a disadvantage in patients with lung disorders in diagnostic studies, it may be an advantage in therapeutic applications with radionuclides which have long physical half lives.     

The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenan-induced paw oedema of rat

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation. On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal disorders as a complementary therapy. In this study, the effects of both topical capsaicinoids-containing patch and local subcutaneous capsaicin application on the anti-inflammatory action of NSAID were examined. Carrageenan-induced paw oedema of rats was used as the inflammation model. The volume and weight of the paw oedema and plasma extravasation in the paw were determined after carrageenan injection. The systemic application of diclofenac (3 mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema. Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20 μg/paw) alone did not cause any effect on oedema volume and weight. However, the combination of diclofenac with topical capsaicinoids-containing patch significantly increased the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents plasma extravasation was decreased by capsaicinoids-containing patch with and without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The results of this study indicate that topical application of capsaicinoids-containing patch enhances the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to its capsaicin content. In the treatment of local inflammatory disorders, the combination of NSAID with topical capsaicinoids-containing patch could increase the anti-inflammatory efficiency of drug without systemic side effects.     

Efficacy and safety of non-laser, targeted UVB phototherapy alone and in combination with psoralen gel or calcipotriol ointment in the treatment of localized, chronic, plaque-type psoriasis

Background Topical drugs enhance the therapeutic effects of ultraviolet (UV)‐based therapy for psoriasis. However, their efficacy has yet to be established in a clinical trial. Objectives This study aimed to compare the efficacy of targeted microphototherapy alone and in combination with psoralen or calcipotriol in the treatment of plaque‐type psoriasis. Methods Thirty individuals, affected by plaque‐type psoriasis, were treated with targeted narrowband UVB phototherapy alone (Group 1), in combination with psoralen gel (Group 2), or in combination with calcipotriol ointment (Group 3) three times per week based on predetermined minimal erythema doses for 10 weeks. Results All patients in each group completed the study. The percentages of improvement in Psoriasis Area and Severity Index (PASI) and Psoriasis Severity Index (PSI) scores were 33.9% and 38.3% in Group 1, 29.9% and 29.8% in Group 2, and 67.2% and 59% in Group 3, respectively. There was no statistically significant difference in improvement between Groups 1 and 2 (P > 0.05). Outcomes in Group 3 were found to be superior compared with those in the other groups. Conclusions The addition of calcipotriol ointment in targeted phototherapy enhances the therapeutic effects of phototherapy in the treatment of plaque‐type psoriasis.