Involvement of Hepatic Stimulator Substance in Experimentally Induced Fibrosis and Cirrhosis in the Rat

Liver fibrosis results from sustained wound healing response to chronic liver injury. Liver cirrhosis, the end stage of the fibrotic process, is characterized by disruption of the entire liver architecture and reduced hepatocyte regenerative ability. Hepatic stimulator substance (HSS) is a liver-specific growth factor triggering hepatocyte proliferation in vitro and in vivo. Previous studies have indicated the involvement of HSS in animal models of acute liver injury. The aim of the present study was to investigate the involvement of HSS in the process of fibrosis and cirrhosis induction. Liver fibrosis and cirrhosis were induced in rats by thioacetamide (TAA) administration (300 mg/l) in the drinking water for 3 months, and animals were killed at 0, 1, 2, and 3 months of treatment. TAA administration resulted in progressively increasing liver fibrosis, leading to the onset of cirrhosis at the end of the experimental time. HSS was continuously produced during the course of fibrosis and cirrhosis induction, peaking at the 2nd month of TAA treatment, coinciding with markers of hepatic proliferative capacity, as thymidine kinase activity and DNA biosynthesis. Significantly reduced HSS activity was noted in cirrhotic liver (3rd month). In this case, the exogenous HSS administration during the 3rd month of TAA treatment suppressed the onset of liver cirrhosis, stimulating the hepatic regenerative capacity. Our data indicate the active participation of HSS in the process of fibrosis and cirrhosis induction post-TAA treatment in rats, suggesting also the beneficial effect of HSS treatment against cirrhosis induction with future possible clinical implications.     

Excited-state dynamics in photosystem II: Insights from the x-ray crystal structure

The heart of oxygenic photosynthesis is photosystem II (PSII), a multisubunit protein complex that uses solar energy to drive the splitting of water and production of molecular oxygen. The effectiveness of the photochemical reaction center of PSII depends on the efficient transfer of excitation energy from the surrounding antenna chlorophylls. A kinetic model for PSII, based on the x-ray crystal structure coordinates of 37 antenna and reaction center pigment molecules, allows us to map the major energy transfer routes from the antenna chlorophylls to the reaction center chromophores. The model shows that energy transfer to the reaction center is slow compared with the rate of primary electron transport and depends on a few bridging chlorophyll molecules. This unexpected energetic isolation of the reaction center in PSII is similar to that found in the bacterial photosystem, conflicts with the established view of the photophysics of PSII, and may be a functional requirement for primary photochemistry in photosynthesis. In addition, the model predicts a value for the intrinsic photochemical rate constant that is 4 times that found in bacterial reaction centers.     

The presence of insomnia and depression contributes to the acceptance of an initial treatment trial of continuous positive airway pressure therapy in patients with obstructive sleep apnea

Sleep and Breathing - The presence of comorbid insomnia and sleep apnea (COMISA) reduces the initial acceptance of continuous positive airway pressure (CPAP) therapy in 39–58% of patients...     

A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria

Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.     

Predictors of impaired quality of life in patients with rheumatic diseases

Quality of life (QoL) is a complex outcome and rheumatologic patients typically exhibit several comorbidities with a negative impact. In this study, we analyzed with respect to QoL for the first time a wide range of physical and psychological factors, including individual, clinical and disease-related parameters, mental health disorders, sexual dysfunction, and cardiovascular comorbidities among consecutive rheumatologic patients. QoL was evaluated using the EuroQol 5D (EQ-5D) utility index. The Health Assessment Questionnaire (HAQ) Disability Index, and the HAQ Pain Visual Analogue Scale were used as measures of physical disability and arthritis-related pain, respectively. The Hamilton Anxiety Scale and Zung Self-Rating Depression Scale, the International Index of Erectile Function and the Female Sexual Functioning Index were completed by all patients. In total, 360 patients were included, 301 females and 59 males. In the univariate analysis, pain, physical disability (p?<?0.001 for both), disease duration (p?=?0.014), anxiety and depression (p?<?0.001 for both), as well as sexual dysfunction (p?=?0.001 for females, p?=?0.042 for males), correlated with QoL. Female sex (p?<?0.001), advanced age (p?=?0.029), lower educational level (p?=?0.005), and cardiovascular factors (hypertension, dyslipidemia, diabetes, lack of systemic exercise) also appeared to negatively affect QoL. However, in the multiple regression model, only anxiety, pain, physical disability (p?<?0.001 for all), and disease duration (p?=?0.019) remained significant predictors of QoL. The emotional side and the disease-related physiological mode of rheumatic diseases appear as major independent correlates of QoL among rheumatologic patients, who may thus benefit the most from combined supportive psychological and pain-relieving interventions.     

The changing sella: internal carotid artery shift during transsphenoidal pituitary surgery

Purpose

Injuries to the internal carotid artery (ICA) are potentially lethal complications in transsphenoidal surgery (TSS) for pituitary lesions. The intercarotid distance (ICD) is thus a major parameter, determining the width of the surgical corridor in TSS. The purpose of the study is to investigate changes in ICD at different levels of the ICA during and after TSS using high definition intraoperative MRI (3T-iMRI).

Methods

Pre-, intra- and 3 months postoperative MRI images of 85 TSS patients were reviewed. ICD was measured at the horizontal (ICDC4h) and vertical (ICDC4v) intracavernous C4 segment as well as at the C6 segment (ICDC6). Association between ICD change at different levels and time points were compared and potential factors predicting ICD reduction were analyzed.

Results

ICD decreased intraoperatively at all three segments of ICA by ?3% (median decreases: ICDC4h: ?0.5 mm, ICDC4v: ?0.7 mm ICDC6: ?0.4 mm). At 3 months postoperative MRI, ICD reduced by a further ?4%, ?2% and ?4% respectively (median decreases ICDC4h: ?0.7, ICDC4v: ?0.4 mm, ICDC6: ?0.5 mm). Postoperative narrowing in ICD occurred independent of further resection after 3T-iMRI. ICD change correlated between different levels of the ICA indicating a uniform shift perioperatively. Preoperative ICD was significantly associated with the intraoperative reduction in ICDC4v and ICDC6.

Conclusions

We have demonstrated a uniform narrowing in ICD at different levels of the ICA during and after TSS adenoma resection. Surgeons should be aware of this change since it determines the width of the surgical corridor and can thus influence the ease of surgery.

     

Anti-ribonucleoprotein antibodies mediate enhanced lung injury following mesenteric ischemia/reperfusion in Rag-1(-/-) mice

Natural Abs and autoantibodies bind antigens displayed by ischemia-conditioned tissues, followed by complement activation and enhanced tissue injury during reperfusion. Anti-ribonucleoprotein (RNP) Ab is associated with lung disease in patients with autoimmune disease but it is not known whether these abs contribute to lung injury. Mesenteric I/R in mice leads to local and remote lung injury. Accordingly, we used this model to investigate whether anti-RNP Abs would reconstitute I/R damage with prominent lung damage in injury-resistant Rag1(-/-) animals. Rag1(-/-) mice injected with anti-RNP Ab containing serum and subjected to mesenteric I/R suffered greater intestinal injury than control-treated and sham-operated animals. The magnitude of the reconstituted damage was anti-RNP Ab titer-dependent. Anti-RNP Ab-treated animals demonstrated a dose-dependent increase in lung histologic injury scores compared to control and sham animals. Anti-RNP mediated injury was shown to be complement dependent. These experiments reveal a novel mechanism whereby anti-RNP Abs contributes to the development of pulmonary pathology in patients with autoimmune diseases following exposure of remote organs to I/R injury.     

Evaluation of different PCR assays for early detection of acute and relapsing brucellosis in humans in comparison with conventional methods

Human brucellosis is a significant public health problem in many Mediterranean countries including Greece. The conventional serological methods, as well as blood cultures, have serious limitations, especially in chronic, relapsing, and focal forms of the disease. Four different PCR assays were applied in 4,926 buffy coat, whole-blood, and serum samples received from 200 patients admitted with brucellosis to the Infectious Diseases Hospital, Thessaloniki, Greece, for the rapid diagnosis of acute infection and relapses and compared to blood culture and serological tests (i.e., Wright's seroagglutination test, Coombs' antibrucella test, and the complement fixation test). The four PCR assays had excellent sensitivity and specificity and were able to detect all of the cases of acute disease. Buffy coat and whole blood were the optimal specimens. All four PCR assays were negative in all follow-up samples from 183 patients who had completed a successful treatment and were positive in all follow-up samples from 17 patients who had relapses in the first year after therapy, including the times of the relapses. In conclusion, PCR is a very useful tool for the rapid diagnosis of acute brucellosis and a good marker for the posttreatment follow-up and the early detection of relapses.