Biologics for psoriasis: What is new?

Etiology of psoriasis is unclear but environmental, genetic, and immune factors act significant roles in the pathogenesis of this disease. Helper T cells (TH), plasmoid, and dermal dendritic cells play a prominent role in the development of classical psoriatic lesions. Interleukin stimulation is another important process in the pathogenesis of the disease that directly influences keratinocytes and leading to the formation of psoriatic pattern in the skin. Tumor necrosis factor (TNF) α which releases from keratinocytes activates dendritic cells in the early stages of complex pathogenesis of psoriasis. Activated keratinocytes also produce other proinflammatory cytokines (IL‐1b and IL‐6), antimicrobial peptides, and various chemokines. TNF activates dendritic cells that produce IL‐23, leading to TH17 differentiation. TH17 cells secrete IL‐17A, which has been shown to promote psoriatic skin changes. Consequently, after clarification of these main pathological mechanisms, anti‐IL therapies have been accepted as a major treatment for patients with moderate‐to‐severe psoriasis. Here, actual information will be presented about biological agents currently in clinical use or being tested for clinical application for treatment of patients with psoriasis.     

Apparent diffusion coefficient measurements in the hippocampus and amygdala of patients with temporal lobe seizures and in healthy volunteers

PURPOSE: The goals of this work were to measure the apparent diffusion coefficients (ADCs) for both hippocampus and amygdala of persons diagnosed with temporal lobe epilepsy (TLE) and unilateral hippocampus pathology on magnetic resonance imaging and to evaluate the sensitivity of diffusion-weighted (DW) images in determination of the lateralization of the epileptogenic focus. METHODS: Thirteen cases with a TLE diagnosis and 21 healthy subjects were evaluated. Fluid-attenuated inversion recovery and T2W images of TLE cases revealed hippocampal volume loss and signal intensity changes. DW images were obtained by spin-echo echo-planar sequences vertical to the hippocampal axis. Qualitative and quantitative ADCs for left and right hippocampus and the amygdala of the controls and the patients were determined. Hippocampal ADCs were obtained independently at the head, body, and tail levels of the hippocampus. Statistical evaluation was conducted with Kruskal-Wallis and Mann-Whitney U tests. Predictive cutoff levels of hippocampal ADCs for identifying pathologic areas were established through receiver operating characteristic (ROC) curve analysis. RESULT: On conventional images, 5 of 13 cases had right hippocampal pathology, and 8 of 13 cases had left hippocampal pathology. There were no bilateral hippocampal changes in signal intensity and no cases with bilateral atrophy. The amygdala was normal in all patients except one case of hyperintense signals. No statistical differences were found between the hippocampal and amygdaloid ADCs of the control subjects (P > 0.05). However, there was a significant difference between the ADCs for the side with hippocampal pathology and the ADCs for the contralateral side, and the control group (P < 0.001). No statistical difference was detected for the amygdala (P > 0.05). Hippocampal and amygdaloid ADCs of the contralateral lesion and the values of the control group were not statistically significantly different (P > 0.05). ROC curve analysis indicated 136 as the best cutoff level for hippocampal pathology. CONCLUSION: DW trace images are insensitive in lateralization of hippocampal pathology; however, lateralization can be achieved through ADC measurements of the hippocampus. An increase in ADC on the affected side should be considered as indicating pathology. On the other hand, amygdaloid ADC values remain inaccurate.     

Comparison of retinal nerve fiber layer and macular thickness measurements with Stratus OCT and OPKO/OTI OCT devices in healthy subjects

AIM: To compare retinal nerve fiber layer (RNFL) and macular thickness measurements obtained with the Stratus optical coherence tomography (OCT) and OPKO/OTI OCT devices. METHODS: Included in the study were 59 eyes of 30 participants. All measurements for each eye were done on the same day with both devices. Student’s paired t-tests were used to compare the central macular thickness and RNFL measurements of the Stratus OCT and OPKO/OTI OCT. Pearson correlation was used to assess the relationship between the devices. Coefficient of variation (COV) was calculated to assess intersession repeatability. RESULTS: Using both the Stratus OCT and OPKO/OTI OCT, respectively, the measured mean average RNFL thicknesses were 98.9±11.1 μm and 115.1±9.6 μm (P=0.001), and the measured mean central retinal thicknesses (CRT) were 196.2±18.8 μm and 204.5±21.1 μm (P<0.001). Measured by the two devices, the RNFL thickness values were correlated in all quadrants, as were the retinal thickness values except the inferior outer sector. COV for average RNFL and CRT thickness were 2.9% and 4.6% for Stratus OCT, and 2.1% and 4.2% for OPKO/OTI OCT, respectively. CONCLUSION: We found good reproducibility of RNFL and retina thickness measurements for both Stratus OCT and OPKO/OTI OCT devices. However, even though the two OCT systems provided statistically correlated results, the values for both RNFL and macular thickness were statistically different. RNFL and macular thickness measurements with the OPKO/OTI OCT were higher than that of the Stratus OCT; therefore, the two OCT systems cannot be used interchangeably for the measurements of RNFL and macular thickness.     

Novel Antiinflammatory Analgesics: 3-(2-/4-Pyridylethyl)-Benzoxazolinone and Oxazolo[4,5-β]pyridin-2-one Derivatives

Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives have been synthesized by reacting 2-and/or 4-vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one. Their chemical structures have been proven by IR, ¹H-NMR, ¹³C-NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster′s Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2 .     

Electrochemical potentials during radiofrequency energy delivery: a new method to control catheter ablation of arrhythmias.

AIMS: Thermal injury of subendocardial tissue leads to a release of electrolytes and free radicals from the intracellular site creating a change in electrochemical potential (eP) between the distal and the proximal catheter tip electrodes. The aim of the study was to verify the detection of ablation-induced release of electrolytes and free radicals and to assess the suitability of control-line energy delivery at ablation by measuring eP. METHODS AND RESULTS: In vitro tests under constant flow conditions were performed in a 101 bath of physiological saline solution or bovine blood. Endomyocardial preparations of fresh bovine hearts were used. Closed-loop temperature-controlled, irrigated and closed-loop eP-controlled ablations were performed. In vivo animal investigations were performed in six anaesthetized and ventilated pigs. The existence of the eP was established in the tank model and was confirmed in animal investigations. High correlations were found between eP and catheter tip temperature (r=0.87) and between maximum eP and induced lesion size (r=0.85). Also a high correlation (r=0.85, P<0.001) was found between eP and lesion volume. CONCLUSIONS: Control of energy delivery during RF ablation by the measurement of eP is feasible. In comparison with temperature controlled RF ablation, ablation guided by eP-measurement revealed a superior correlation with induced lesion size. Especially during cooled radiofrequency catheter ablation eP is the only parameter for control of energy delivery.     

The Restorative Effect of Gallic Acid on the Experimental Sciatic Nerve Damage Model

ObjectivePeripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects. MethodsThirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated. ResultsCompared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group. ConclusionGallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.     

The effect of retinyl palmitate on healing of benign vocal fold lesions

The leading cause of vocal fold lesions such as nodules and polyps is phonotrauma, which causes microhematoma formation in the vocal fold cover that can initiate an inflammatory process. Vitamin A (Vit A) is essential for immunity, cellular differentiation and maintenance of respiratory epithelium. The aim of this study is to investigate the effect of Vit A (retinyl palmitate) on healing of vocal fold lesions, including vocal polyps and nodules. Eighteen patients with vocal fold lesions were included in the study. Of the patients, 13 had vocal polyps and 5 had vocal nodules. Patients received 90,000 IU oral Vit A in palmitate form daily for 2 months. In addition to Vit A treatment, only vocal hygiene recommendations were given to the patients, without any other medication or specific voice therapy. Pre- and post-treatment acoustic analysis [jitter % (jitt %), shimmer % (shim %), normalized noise energy (NNE), maximum phonation time (MPT), etc.] were performed. Lesion dimensions and stroboscopic findings were evaluated. Voice handicap index (VHI) was applied. Statistical analysis was performed between pre- and post-treatment measurements. Of the 18 patients, 8 had immature lesions (6 polyp-like lesions and 2 immature nodules) and 10 had mature lesion (7 polyps and 3 nodules). None of the patients showed complete healing. Partial response was seen in four patients with immature lesions. There were minimal changes in lesion dimensions, but this difference did not reach statistical significance. MPT of patients with immature lesions were close to significance level but overall MPT revealed no significant improvement (p = 0.051). Jitt %, shim % and NNE did not change significantly. In this study, the only statistically significant finding was VHI of the patients with immature lesions. Three of the patients complained of weight gain. Our data showed that Vit A at a given level of dose and duration seems to be ineffective in the treatment of benign vocal fold lesions. On the other hand, whether Vit A is effective on mature and immature lesions of vocal folds at higher doses and/or longer duration of treatment or not requires further studies.     

Pegylated interferon therapy during early pregnancy for hepatitis B infection: does it prevent vertical transmission?

In general, interferon (IFN) is avoided during pregnancy due to the possibility of fetal side effects. We, herein, reported two child-bearing women with chronic hepatitis B (HB) infection who used pegylated interferon alfa 2b (PEG IFNα 2b) in first trimester unintentionally. We compared HB contracting rates of gestations in which IFN was used and not used. The cases are unique in that they could highlight the importance of IFN use in early gestation for preventing vertical transmission particularly if combined with antiviral therapy for the rest of pregnancy.