Pyoderma gangrenosum and exacerbation of psoriasis resulting from pegylated interferon alpha and ribavirin treatment of chronic hepatitis C

Interferon therapy is the cornerstone of chronic hepatitis C treatment. Side effects of interferon include possible triggering or exacerbation of immune diseases in consequence of immunomodulatory effects. We describe the unique case, in which pyoderma gangrenosum and exacerbation of psoriasis were developed 8 weeks after pegylated interferon alpha 2a and ribavirin therapy in a 45-year-old woman. The therapy had to be stopped on account of pyoderma gangrenosum and exacerbation of psoriasis in spite of a biochemical response to the therapy for hepatitis C. The evolution was favorable after stopping treatment. Therefore, we propose this would suggest a possible autoimmune mechanism for the development of pyoderma gangrenosum and exacerbation of psoriasis with pegylated interferon therapy. A susceptible patient, who has an autoimmune disease before interferon therapy, had to be informed that interferons may induce de novo or exacerbate existing immune diseases by immunomodulatory actions. To the best of our knowledge, this is the first case report of pyoderma gangrenosum and psoriasis that resulted from pegylated interferon alpha 2a and ribavirin treatment of chronic hepatitis C.     

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 ± 1.9 vs 5.0 ± 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.     

Statistical shape analysis of the rat hippocampus in epilepsy

In this study, we aimed to (1) propose landmarks for the hippocampus in a rat brain using an experimental study and (2) investigate hippocampus shape changes in a rat brain with epilepsy using the statistical shape analysis method. We have used the statistical shape analysis method to illustrate hippocampal shape deformation due to epilepsy. Statistical shape analysis is of increasing interest to the neuroimaging community because of its potential for locating morphological changes. Nineteen rat brains (ten healthy and nine epileptic) with hematoxylin and eosin images of the hippocampus were used. The results strongly indicated that the normalized hippocampal shape of the epileptic group was different from the nonepileptic group; deformation was seen most significantly in the medial regions of the cornu ammonis (CA1 and CA3) of the hippocampus. In conclusion, our landmark-based methodology detected regional differences in the hippocampus in epilepsy. This study may serve as an initial reference for future studies on shape alteration of the hippocampus associated with certain medical conditions.     

Free radical damage as a biomarker of bladder dysfunction after partial outlet obstruction and reversal

OBJECTIVE

To investigate the use of free‐radical generation as a result of protein carbonylation and nitrotyrosination to characterize the level of bladder dysfunction after partial bladder outlet obstruction (PBOO) and reversal.

MATERIALS AND METHODS

We surgically created PBOO in male New Zealand White rabbits; after 4 weeks of PBOO, one group of six rabbits was assessed, while the PBOO was relieved in two additional groups of six rabbits each that were assessed at 4 and 8 weeks after relieving the PBOO. Six sham‐operated rabbits served as controls. Sedated rabbits were assessed by cystometry and the bladders were then removed for contractile, histological and molecular studies. Western blotting was used to determine the level of carbonylation and nitrotyrosination at the protein level.

RESULTS

The PBOO group had significant decreases in the contractile responses to field stimulation, ATP, carbachol and KCl. The responses to all forms of stimulation increased significantly at 4 weeks after reversal, and further increased to near normal levels by 8 weeks. Similarly, compliance and cystometric values also returned to near normal values after reversal. The hypertrophied smooth muscle of the obstructed bladders regressed to near‐normal size. There was a significant increase in the level of carbonylation and nitrotyrosination after PBOO, and a progressive decrease in the 4‐week reversal groups, nearing control values by 8 weeks.

CONCLUSIONS

Significantly increased carbonylation and nitrotyrosination levels after PBOO correlated with the severe dysfunction in the obstructed rabbits. Similarly, decreased levels of oxidation and nitration correlated with the functional recovery after reversal.     

Focal fibrocartilaginous dysplasia in the humerus

Focal fibrocartilaginous dysplasia is an uncommon, benign bone lesion that causes deformity of the long bones in young children. It has most commonly been encountered in the proximal tibia, and very rarely in the long bones of the upper limb, that is, the proximal humerus, distal radius, ulna, and proximal phalanx. Only one case of focal fibrocartilaginous dysplasia of the proximal humerus has been reported previously. The present study reports two such additional cases that were diagnosed in late childhood. The clinical presentation and radiographic findings are described with an emphasis on the natural evolution of the disease. Limb-length discrepancy is anticipated in these children in the long-term follow-up and, therefore, surgical intervention should be considered in the treatment.     

<Emphasis Type="Italic">Morganella morganii</Emphasis>-associated arthritis in a diabetic patient

This case report involves a 60-year-old diabetic man who developed septic arthritis as a result of the pathogen Morganella morganii. The patient had complaints of elevated body temperature, malaise, rigors and pain in the left knee, despite no history of trauma. On examination of the knee, erythema, warmth, tenderness and swelling was observed. Arthrocentesis performed on his left knee indicated the presence of straw-coloured, cloudy fluid without crystals. Bacterial identification based on biochemical and automated methods indicated the growth of M morganii. M morganii was also isolated sedimentafrom the exudate of a diabetic ulcer in the left foot, with antibiotic susceptibilities identical to those from the knee effusion. This case indicates that M morganii may be considered as a possible cause of septic arthritis in diabetic patients, especially those with diabetic foot infections.     

Changes in the smooth muscle of the corpora cavernosum related to reversal of partial bladder outlet obstruction in rabbits

Previous studies have demonstrated that partial bladder outlet obstruction (PBOO) in the rabbit induces an increase in corpus cavernosum smooth muscle (CCSM) tone, which may make it difficult for the CCSM to relax. Thus, to determine whether the corpus cavernosum restores relaxation after reversal of PBOO, we investigated the physiologic, histologic, and cell biology in penises obtained from rabbits 4 weeks and 8 weeks after reversal of PBOO. CCSM from bladder outlet-obstructed and obstruction-reversed rabbits showed significant decreases in the contractile responses to phenylephrine. The relaxation responses to electrical field stimulation (EFS), ATP, acetylcholine, and sodium nitroprusside (SNP) were decreased in obstructed and reversed for 4 weeks groups. By 8 weeks of reversal, the relaxation of CCSM was increased gradually in response to EFS, SNP, and acetylcholine. However, the response to ATP did not result in the relaxation of CCSM to control levels. The ratio of SM to collagen decreased after obstruction and remained low after reversal. Expression of both isoforms of Rho kinase (ROK) was increased in obstruction groups. At 4 weeks of reversal, the expression of ROK alpha remained at obstruction level, whereas ROK beta expression decreased in comparison with the obstruction group. By 8 weeks of reversal, expression of both ROK alpha and beta significantly decreased when compared with the obstruction group. These results suggested that the poor relaxation response at reversal of 4 weeks was associated with incomplete decreased expression of both isoforms of ROK, whereas the incomplete recovery of the CCSM relaxation response at reversal of 8 weeks may be associated with structural alterations in the CC and irreversible damage from PBOO.     

Protective effect of erythropoietin pretreatment in testicular ischemia-reperfusion injury in rats

Background/Purpose

This study was designed to investigate the effects of recombinant erythropoietin (EPO), a hormone widely used for treatment of uremic anemia, in rats subjected to testicular ischemia and reperfusion (I/R).

Methods

Thirty-five male rats were divided into the following: control, sham operated, ischemia (I), I/R, and I/R + EPO groups. In the I group, 2 hours of left unilateral testicular torsion were performed, and in the I/R and I/R + EPO groups, an additional 2 hours of testicular detorsions were performed. The I/R + EPO group was pretreated intraperitoneally with EPO (500 IU/kg) before reperfusion. Testicular tissue samples were examined for biochemical and histopathologic parameters. Apoptotic cells in all testes were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling technique and caspase 3 immunohistochemistry.

Results

At histopathologic examination, ischemic changes in primary spermatocytes were noted in all torted testes. Cellular damage and apoptosis were more severe in ischemic groups than the EPO-pretreated group. There were statistically significant differences in tissue biochemical parameters in the I and I/R groups compared with the I/R + EPO group.

Conclusions

The results of the present study suggest that EPO exerts protective effects against I/R injury via the modulation of free radical scavenger's activities, which decreases lipid peroxidation levels and attenuation of apoptosis.     

Effect of 3-amino benzamide, a poly(adenosine diphosphate-ribose) polymerase inhibitor, in experimental caustic esophageal burn

Introduction

The enzyme poly(adenosine diphosphate-ribose) polymerase affects the repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. This study was designed to investigate the efficacy of 3-amino benzamide (3-AB), a poly(adenosine diphosphate-ribose) polymerase inhibitor, on the prevention of esophageal damage and stricture-formation development after esophageal caustic injuries in rat.

Materials and Methods

Forty-five rats were allocated into 3 groups: sham-operated, untreated, and treated groups. Caustic esophageal burn was created by instilling 15% NaOH to the distal esophagus. The rats were left untreated or treated with 3-AB 10 mg/kg per day intraperitoneally. All rats were killed on the 28th day. Efficacy of the treatment was assessed by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and protein carbonyl content (PCC) in esophageal homogenates.

Results

Treatment with 3-AB decreased the stenosis index and histopathologic damage score seen in caustic esophageal burn rats. Hydroxyproline level was significantly higher in the untreated group as compared with the group treated with 3-AB. Caustic esophageal burn increased MDA and PCC levels and also decreased SOD and GPx enzyme activities. On the contrary, 3-AB treatment decreased the elevated MDA and PCC levels and also increased the reduced SOD and GPx enzyme activities.

Conclusion

3-Amino benzamide has a preventive effect in the development of fibrosis by decreasing tissue damage and increasing the antioxidant enzyme activity in an experimental model of corrosive esophagitis in rats.