Hematopoietic cell activation in the subventricular zone after Theiler's virus infection

Background

The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis.

Method

Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes.

Results

Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex.

Conclusion

The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.     

CHILDHOOD CHRONIC RENAL FAILURE IN QATAR

Thirty children below the age of 12 with chronic renal failure (CRF) were studied. In 21 patients (70%) the renal failure was secondary to congenital or familial aetiology. Obstructive uropathy (53.3%), mostly due to posterior urethral valves (40%), comprised the majority of cases. Four cases (13.3%) were secondary to reflux nephropathy. It is concluded that the majority of cases of CRF in the state of Qatar are secondary to potentially treatable or preventable conditions. Use of antenatal ultrasonography combined with aggressive management of obstruction and urine infection may help reduce morbidity and mortality.     

Nitroxyl (HNO) for Treatment of Acute Heart Failure

The loss of contractile function is a hallmark of heart failure. Although increasing intracellular Ca²⁺ is a possible strategy for improving contraction, current inotropic agents that achieve this by raising intracellular cAMP levels, such as β-agonists and phosphodiesterase inhibitors, are generally deleterious when administered as long-term therapy due to arrhythmia and myocardial damage. Nitroxyl donors have been shown to improve cardiac function in normal and failing dogs, and in isolated cardiomyocytes they increase fractional shortening and Ca²⁺ transients, independently from cAMP/PKA or cGMP/PKG signaling. Instead, nitroxyl targets cysteines in the EC-coupling machinery and myofilament proteins, reversibly modifying them to enhance Ca²⁺ handling and myofilament Ca²⁺ sensitivity. Phase I–IIa trials with CXL-1020, a novel pure HNO donor, reported declines in left and right heart filling pressures and systemic vascular resistance, and increased cardiac output and stroke volume index. These findings support the concept of nitroxyl donors as attractive agents for the treatment of acute decompensated heart failure.     

IGF-IR: potential role in antitumor agents

As insulin-like growth factor (IGF) signaling has been recognized to play an important role in human cancer, the IGF-I receptor (IGF-IR) is currently the focus of intensive research aimed at developing novel antitumor agents. The IGF system is frequently deregulated in cancer cells by the establishment of autocrine loops involving IGF-I or -II and/or IGF-IR over-expression. Moreover, epidemiological studies have suggested a link between elevated IGF levels and the development of major human malignancies, such as breast, colon, lung and prostate cancer. Experimental therapies aimed at inhibiting IGF signaling in human tumors involve various approaches, including neutralizing antibodies and pharmacological inhibitors of IGF-IR kinase activity. Although there are numerous reports describing the antitumor activity of such agents against human cancer cell lines propagated in vitro or in experimental animals, it remains unclear how soon the existing drugs will have a demonstrable effect in patients. In this review, we will discuss the evidence implicating the IGF signaling system in the pathology of human cancer and the various strategies that have so far been developed to target the IGF-IR.     

纤维胆道镜临床应用160例

0　引言　纤维胆道镜 (下称胆道镜 )在肝内外胆道疾病中的应用 ,其诊治价值已得到充分肯定 .我院 1996 - 0 1/ 1999- 12 ,术中、术后使用胆道镜诊治胆道肿瘤及结石 16 0例 ,取得了较满意的效果 .1　对象和方法1.1　对象　术中应用胆道镜行胆道探查共 38(男 2 3,女 15 )例 ,其中胆总管结石 2 9例 ,肝内胆管多发结石 5例 ,胆管肿瘤4例 .术后经 T管瘘道取石或活检 12 2 (男 78,女 44 )例 ,年龄18～ 77岁 ,其中肝外胆管残余结石 114例 ,多发性肝内胆管残余结石 5例 ,胆总管下端肿瘤活检 2例 ,置管造影 1例 .1.2　方法　日本 Olympus CHP2 OQ…     

Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease

Background and aimTo explore associations between serum 25-hydroxyvitamin D₃ [25(OH)D] concentrations and liver histology in patients with non-alcoholic fatty liver disease (NAFLD).Methods and resultsWe studied 60 consecutive patients with biopsy-proven NAFLD, and 60 healthy controls of comparable age, sex and body mass index (BMI).NAFLD patients had a marked decrease in winter serum 25(OH)D concentrations (51.0 ± 22 vs. 74.5 ± 15 nmol/L, P < 0.001) compared with controls. Metabolic syndrome (MetS; as defined by the Adult Treatment Panel III criteria) and its individual components occurred more frequently among NAFLD patients. The marked differences in 25(OH)D concentrations observed between the groups were little affected by adjustment for age, sex, BMI, creatinine, calcium, homeostasis model assessment (HOMA)-insulin resistance, and the presence of the MetS. Interestingly, among NAFLD patients, decreased 25(OH)D concentrations were closely associated with the histological severity of hepatic steatosis, necroinflammation and fibrosis (P < 0.001 for all) independent of age, sex, BMI, creatinine, calcium, HOMA-insulin resistance, and presence of the MetS.ConclusionsCompared with controls, NAFLD patients have a marked decrease in serum 25(OH)D concentrations, which is closely associated with histopathological features of NAFLD. Further investigation into whether vitamin D₃ may play a role in the development and progression of NAFLD appears to be warranted.