Adverse Effects Of Long-term Administration Research Articles

Microbiology of diabetic foot osteomyelitis – Is it geographically variable?

IntroductionDiabetic foot osteomyelitis (DFO) is a dreaded complication as both diagnosis and treatment of the condition is laborious. However, for proper decision on antibiotics in medical management of DFO, accurate determination of microbes is necessary to narrow the spectrum of coverage and to reduce adverse effects of long-term administration of antibiotics. With differing pattern of use of antimicrobials and their resistance pattern in different countries, it is empirical to determine the microbiological characteristics of bone cultures in DFO from a referral institute in South India. Materials and MethodsThis study was a retrospective chart review of all cases of proven DFO who had consented for debridement and bone culture or those who underwent amputation. Both deep soft tissue (DST) and bone cultures were obtained for aerobic bacteria. Clinical characteristics and site(s) of DFO were recorded. Investigations for peripheral artery disease were performed if clinically indicated. ResultsIn all, 105 patients with DFO were reviewed. Mean age was 62 years and 70% were men. Of those who were screened, 57% had evidence of peripheral arterial disease by arterial doppler. 46% of bone culture samples were sterile. Gram- negative organisms were more common (58%). Following staphylococcus, pseudomonas was the second common isolate. Of total staphylococcal isolates 37% were MRSA and 33% of klebsiella isolates were ESBL producing. Concordance rate between DST and bone cultures was 66%. 90% were mono-bacterial isolates. The commonest site of involvement of DFO was terminal phalanges of toes rather than base of 1st metatarsal. ConclusionWidespread use of antibiotics, tropical climate and route of entry of organisms causing DFO differed in our cohort of patients. Further studies from different regions of world would shed light onto different pattern of microbes causing DFO.

Adverse effects of long-term administration of fluvoxamine on haematology, blood biochemistry and fertility in male albino rats: a possible effect of cessation.

Fluvoxamine is recommended as first-line treatment for a number of obsessive-compulsive disorders, anxiety disorders, social phobia, and post-traumatic stress disorder and panic disorder. The adverse effects of prolonged oral administration of fluvoxamine on haematology, biochemical parameters and fertility in male rats were evaluated in this study. Sixty adult male rats were allocated into 5 equal groups and orally treated with fluvoxamine 9mgkg-1 b.wt. (low therapeutic dose, LTD) and 27mgkg-1 b.wt. (high therapeutic dose, HTD), while the control rats received 0.5ml distilled water for a period of 8weeks. The 4th and 5th groups were gavaged with LTD and HTD of fluvoxamine for 8weeks and then left untreated for another 8weeks (recovery groups). HTD of fluvoxamine induced leukocytosis, lymphocytosis and monocytosis. LTD and HTD of fluvoxamine evoked hepatic, renal and cardiac dysfunction. Moreover, fluvoxamine treatment might lead to the risk of male infertility, which is indicated by its deleterious impacts on spermiogram and steroidogenesis hormones. They also induced oxidative stress, apoptosis in testicular tissue. Fortunately, the previous alterations were mostly reversed during the recovery period.

Efficacy of Short-Term FK506 Administration on Accelerating Nerve Regeneration

Background. The slow rate of nerve regeneration following injury can cause extended muscle denervation, leading to irreversible muscle atrophy, fibrosis, and destruction of motor endplates. The immunosuppressant FK506 (tacrolimus) has been shown to accelerate the rate of nerve regeneration and functional recovery. However, the toxic and immunosuppressive properties of FK506 make it undesirable for long-term use. Objective. To take advantage of the regeneration-enhancing effects of FK506 but avoid the potential adverse effects of long-term administration, the current study evaluates and quantifies the efficacy of short-term FK506 treatment in rat models. Methods. Clinically relevant transection and graft models were evaluated, and walking track analysis (WTA) was used to evaluate functional recovery. FK506 was administered for 5 and 10 days post transection injury and 10 and 20 days post graft injury. Both groups involving a short course were compared with the continuous administration group. Results. In the transection model, FK506 was administered for 5 and 10 days postoperatively. WTA demonstrated that 10 days of FK506 administration was sufficient to reduce functional recovery time by 29% compared with negative controls. In the graft model, FK506 was administered for 10 and 20 days postoperatively. Short treatment courses of 10 and 20 days reduced recovery time by 15% and 21%, respectively, compared with negative controls. Analysis of blood–nerve barrier (BNB) integrity demonstrated that FK506 facilitated early reconstitution of the BNB. Conclusions. The results of this study indicate that short-term FK506 delivery following nerve injury imparts a significant therapeutic effect.

Rebamipide Contributes to Reducing Adverse Effects of Long-Term Administration of Omeprazole in Rats

Proton pump inhibitors (PPIs) have become of great importance for the treatment of peptic ulcer disease and gastroesophageal reflux disease. However, these drugs have several adverse effects, including worsening of corpus atrophic gastritis in patients with H. pylori infection, various histological changes including fundic gland-type polyps, inhibition of glycoprotein production, and hypergastrinemia. On the other hand, it has been reported that rebamipide, a gastroprotective drug, has the potential to increase mucous secretion and basically regulate physiological defensive functions aimed to maintain tissue integrity. In this study, we attempted to clarify whether rebamipide improves morphological changes and hypergastrinemia after administration of omeprazole (OPZ) for 1 year in rats. Eight-week-old male Wistar rats were used. Rats were divided into four groups according to diet as follows: 100 mg/kg body weight OPZ group, 100 mg/kg body weight OPZ and 30 mg/kg body weight rebamipide (OPZ + trebanipide group), 30 mg/kg body weight rebamipide, and normal diet (CRF-1). Morphological changes in gastric mucosa in all groups were studied using hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical staining for alpha-amylase. Serum gastrin level and basal acid secretion were also examined. In the OPZ group, cystic degenerations with amorphous eosinophilic contents, decreased mucous secretion, decreased chief cells, and development of pancreatic acinar cell metaplasia were detected. However, in the OPZ+rebamipide group, these morphological changes were significantly milder than in the OPZ group. Serum gastrin level and basal acid secretion in the OPZ group increased significantly compared to those in the control group. But these factors in the OPZ+rebamipide group were almost normalized (similar to those of control animals). In conclusion, long-term OPZ treatment causes various morphological changes, hypergastrinemia, and basal acid hypersecretion. The present results suggest that rebamipide contributes to reducing these adverse effects caused by long-term OPZ treatment in rats.

Effects of Long-Term Oral Administration of Ketoprofen in Clinically Healthy Beagle Dogs

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.