Protective effects of doxycycline in ischemia/reperfusion injury on kidney

Renal ischemia and reperfusion injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. The aim of this study was to evaluate whether doxycycline, a member of the tetracycline family of antibiotics, protects kidney tissue or not. 36 Sprague-Dawley rats (200–250 g) were used. The animals were divided into three groups: control, ischemia/reperfusion and ischemia/reperfusion+doxycycline group. Rats were subjected to renal ischemia by clamping the left pedicle for 1 h, and then reperfused for 1 h. The ischemia/reperfusion+doxycycline group were pretreated intraperitoneally with doxycycline suspension (10 mg/kg) 2 h before the induction of ischemia. Our results indicate that malondialdehyde, matrix-metalloproteinase-2, interleukin-2, interleukin-6, interleukin-10, interleukin 1-beta and tumor necrosis factor-alpha levels were significantly higher in the ischemia/reperfusion group than those in the control group. Doxycycline administration significantly decreased these parameters. Tissue inhibitor of metalloproteinases-1 levels also increased after ischemia/reperfusion and decreased with doxycycline pretreatment, but these changes were not significantly different. Glutathione levels significantly decreased after ischemia/reperfusion injury when compared with the control group and doxycycline pretreatment significantly increased glutathione levels when compared with the ischemia/reperfusion group. Apoptotic cells and p53 positive cells were significantly decreased in doxycycline treated group. These results suggest that doxycycline reduces renal oxidative injury and facilitates repair. Doxycycline may play a role in a renoprotective therapeutic regimen.     

The effect of nasal polyposis related nasal obstruction on cognitive functions

Chronic rhinosinusitis with nasal polyposis is a chronic inflammatory disease of the respiratory mucosa of the nasal cavity and paranasal sinuses. The aim of this study was investigate the effect of nasal obstruction related to chronic rhinosinusitis with nasal polyposis on cognitive functions. Patients with chronic rhinosinusitis with nasal polyposis causing bilateral total or near total nasal obstruction were enrolled in the study. Symptoms of nasal congestion, loss of smell, postnasal drip, headaches, snoring, concentration difficulties and blunted affect were evaluated by Visual Analog Scale. Brief symptom inventory test, Stroop test, visual aural digit span, serial digit learning test and P300 test were used to evaluate cognitive functions. Three months after treatment, the tests done before surgery were repeated and the results were compared. A total of 30 patients were included in the study. On the Visual Analog Scale, all symptoms showed significant postoperative improvement in all patients (p?<?0.001 for all symptoms). Preoperative nasal congestion accompanied with impaired concentration were detected in 27 patients (90%), and these symptoms recovered in all these patients after treatment (p?=?0.035) (correlation coefficient 0.4). Only 22 patients completed the neuropsychological tests. The mean preoperative Stroop test (23.16?±?5.30), visual aural digit span test (24.68?±?3.52), and serial digit learning test (16.18?±?5.35) scores were showed significant improvement compared with mean postoperative Stroop test (21.12?±?5.69), visual aural digit span test (26.45?±?2.98), and serial digit learning test (19.31?±?4.47) scores (p?=?0.047, p?=?0.022, p?=?0.005 respectively). The postoperative P300 latency values improved in 19 (63%) patients. The preoperative and postoperative latency values for P300 showed a significant difference (p?=?0.029), whereas the preoperative and postoperative amplitude values for P300 did not differ (p?=?0.096). In conclusion, the results of this study indicate that chronic rhinosinusitis with nasal polyposis (CRSwNP) has negative effects on cognitive functions, such as the ability to focus and maintain concentration. These cognitive functions improve after the patients undergo endoscopic sinus surgery to treat their CRSwNP.     

Development of a fast and low-cost qPCR assay for diagnosis of acute gas pharyngitis

Background

Group A streptococci (GAS) are the most common bacterial cause of acute pharyngitis and account for 15–30 % of cases of acute pharyngitis in children and 5–10 % of cases in adults. In this study, a real-time quantitative PCR (qPCR) based GAS detection assay in pharyngeal swab specimens was developed.

Methods

The qPCR assay was compared with the gold standard bacterial culture and a rapid antigen detection test (RADT) to evaluate its clinical performance in 687 patients. The analytical sensitivity of the assay was 240 cfu/swab. Forty-five different potential cross-reacting organisms did not react with the test. Four different laboratories for the reproducibility studies were in 100 % (60/60) agreement for the contrived GAS positive and negative swab samples.

Results

The relative sensitivities of the RADT and the qPCR test were 55.9 and 100 %; and the relative specificities were 100 and 96.3 %, respectively. Duration of the total assay for 24 samples including pre-analytical processing and analysis changed between 42 and 55 min depending on the type of qPCR instrument used. A simple DNA extraction method and a low qPCR volume made the developed assay an economical alternative for the GAS detection.

Conclusion

We showed that the developed qPCR test is rapid, cheap, sensitive and specific and therefore can be used to replace both antigen detection and culture for diagnosis of acute GAS pharyngitis.

     

Ultrasonographic and electrophysiologic evaluation of median and ulnar nerves in chronic stroke patients with upper extremity spasticity

Objective: To evaluate the upper extremity nerves of stroke patients morphologically and electrophysiologically and to determine whether there is a relationship between clinical evaluations, ultrasonographic measurements, and electrodiagnostic findings.

Methods: This cross-sectional study included 30 chronic stroke patients. After recording demographical data, clinical, ultrasonographic, and electrophysiological evaluations were performed. Clinical evaluations included Brunnstrom Recovery Stages (BRS), Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), Motricity index (MI), Functional Independence Measurement (FIM), and Functional Ambulation Scale (FAS). For ultrasonographic measurements, median and ulnar nerves were scanned. Median and ulnar nerve conduction studies were performed bilaterally.

Results: Mean ages of the patients were 62.2?±?13.0 years (range 24–84 years; 22 males, 8 females). There was no significant difference in median/ulnar nerve ultrasonographic measurements between paretic and non-paretic sides (p?>?.05), whereas median nerve motor conduction velocity was significantly slower and median nerve F-wave latency was prolonged on the paretic side (p?<?.05). The median and ulnar nerve compound motor action potential (CMAP) amplitudes of paretic sides were positively correlated with lower extremity BRS and FAS scores. Median CMAP amplitudes were also positively correlated with FIM scores and ulnar CMAP amplitudes were positively correlated with motricity scores. Moreover, on the paretic side, there were positive correlations of median SNAP amplitudes with FIM and FAS scores (p?<?.05).

Conclusions: Our results showed electrophysiological changes in peripheral nerves on the paretic upper extremities, however, no morphological change was determined. Further studies with larger number of patients and longer follow-up periods are needed to clarify the effect of stroke and spasticity on the peripheral nervous system.     

Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia–reperfusion injury in rats

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia–reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.     

A Computer-Based Automated Algorithm for Assessing Acinar Cell Loss after Experimental Pancreatitis

The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the “ground truth”). After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1%±0.05% (p = 0.21). Within regions of injured tissue, the software reported a difference of 2.5%±0.04% in acinar area compared with the pathologist (p = 0.47). Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas.     

Distribution and occurrence of the insect pathogenic alga Helicosporidium sp. (Chlorophyta: Trebouxiophyceae) in the predator beetle Rhizophagus grandis G: yll. (Coleoptera: Rhizophagidae)-rearing laboratories

The distribution and occurrence of the insect pathogenic algae Helicosporidium sp. (Chlorophyta: Trebouxiophyceae) in the predator beetle Rhizophagus grandis (Coleoptera: Rhizophagidae)-rearing laboratories were studied and reported here for the first time. The insect pathogenic alga Helicosporidium sp. infection was observed in all R. grandis-rearing laboratories. The infection rate reached more than 20% which is significant among the samples in some R. grandis-rearing laboratories. The infection rates of the examined beetles showed noticeable differences between localities and years. There was no significant difference in the infection levels of male and female beetles. These results showed that Helicosporidium sp. is one of the factors that decrease efficiency of the R. grandis-rearing laboratories.     

Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders,Mild Cognitive Impairment and Alzheimer’s Disease

Background

Cerebrospinal fluid (CSF) α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer’s disease (AD). No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL), to patients with mild cognitive impairment (MCI) and AD.

Methods

Baseline CSF α-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF α-synuclein on regional atrophy rates were tested in 1) four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem), and 2) all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF α-synuclein and diagnosis (testing NL versus MCI, and NL versus AD).

Results

The effects of CSF α-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF α-synuclein, P=0.046) and brainstem (higher atrophy rates in subjects with lower CSF α-synuclein, P=0.063). CSF α-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037) and caudate (P=0.006). Discussion: With the possible exception of caudate and brainstem, the overall weak effects of CSF α-synuclein on atrophy rates in NL, MCI and AD argues against CSF α-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF α-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and reduce CSF α-synuclein levels, respectively.     

Frequencies of four genetic polymorphisms in the <Emphasis Type="Italic">CYP1A2</Emphasis> gene in Turkish population

Cytochrome P450 (CYP) 1A2 gene is involved in the metabolic activation of several carcinogens and altered metabolization of some clinically used drugs. We aimed to investigate the distributions of genetic polymorphisms-3860 (G/A)(CYP1A2*1C) and-2467 (T/del)(CYP1A2*1D) in the 5′-flanking region and-739 (T/G)(CYP1A2*1E) and-163(C/A)(CYP1A2*1F) in the first intron of the CYP1A2 gene in 110 unrelated healthy Turkish volunteers by PCR-RFLP technique. The frequencies of each polymorphism in Turkish population were found as 0.04, 0.92, 0.01, 0.27 for CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, CYP1A2*1F, respectively. Compared with other populations, CYP1A2*1Dhas been found to be significantly increased in Turkish population. On the other hand, in general, the frequencies of the other polymorphisms were concordant with those in the Egyptian and Caucasian populations, and were different from those in the Japanese, Chinese and Ethiopian populations. Our results suggest that due to increased frequency of CYP1A2*1D in Turkish population, unctional significance of CYP1A2*1D should be evaluated. It might be screened to determine the relationship between CYP1A2*1D and CYP1A2 related drug metabolisms in associated groups. This article was submitted by the authors in English.