Absence of the adenosine A2A receptor confers pulmonary arterial hypertension and increased pulmonary vascular remodeling in mice.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by sustained elevation of pulmonary vascular resistance resulting from endothelial and smooth muscle cell dysfunction and collagen deposition in pulmonary vascular walls. In this study, we investigated the role of the adenosine A(2A) receptor (A(2A)R) in the development of PAH by determining the effect of genetic inactivation of A(2A)Rs on pulmonary vascular remodeling in mice. METHODS AND RESULTS: We characterized hemodynamic, histological and ultrastructural changes in pulmonary vascular remodeling in A(2A)R knockout (KO) mice compared with their wild-type (WT) littermates after exposure to normoxia and hypoxic conditions. After exposure to normoxia, compared to WT mice, A(2A)R KO mice displayed: (1) increased right ventricular systolic pressures and an elevated ratio of the right ventricle over left ventricle plus septum (Fulton index), (2) increased wall area and thickness as well as enhanced smooth muscle actin immunoreactivity in pulmonary resistance vessels, (3) increased proliferating cell nuclear antigen-positive cells in pulmonary resistance vessels and (4) increased smooth muscle cells hypertrophy and collagen deposition in the adventitia of pulmonary arteriole walls as revealed by electron microscope. By contrast, histological analysis revealed no features of hypertensive nephropathy in A(2A)R KO mice and there was no significant difference in systemic blood pressure, and left ventricular masses among the 3 genotypes. Furthermore, following chronic exposure to hypoxia, A(2A)R KO mice exhibited exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels and increased cell proliferation in pulmonary resistance vessels, compared to WT littermates. Thus, genetic inactivation of A(2A)Rs selectively produced PAH and associated increased smooth muscle proliferation and collagen deposition. CONCLUSIONS: Extracellular adenosine acting at A(2A)Rs represents an important regulatory mechanism to control the development of PAH and pulmonary vascular remodeling.

[Clinical features of delayed polyneuropathy induced by acute methamidophos toxicosis in 74 cases].

A series of 74 cases of delayed polyneuropathy induced by acute middle to serious toxicosis with Methamidophos is analysed. It consists of 49 males and 25 females aged 12 to 45 years, mean age 22.6 years. The clinical features is similar to those of acute polyneuritis in common. The determination of nerve conduction velocity and electromyography show denervation lesions. The recovery cause is from 0.5 to 2 years. The proposal of the five requirements for diagnosis is listed. It is regarded that the pathogenesis of methamidophos-induced delayed polyneuropathy is the toxic effect produced by the "aging" of the phosphoryl-enzyme complex caused by the phosphorylation of a protein neurotoxic esterase (NTE) in the nervous system, and also is the autoimmuno disorder induced by the "aging" of the NTE being probably an immunological basis.

[Relationship between levamisole and encephalitis syndrome].

The results of a cohort study of 92,346 labour population for probing the relationship between levamisole (LMS) and encephalitis syndrome was reported. There were five patients suffering from the disease in an exposed group (E) of 10,911 people within two months after taking LMS as an anthelmintic for mass treatment, the incidence of the disease is 4.58/10,000. The nonexposed population was divided into two control groups the first group (N1) includes 37,990 people living in the mass treatment villages and the other group (N2) consists of 43,445 people living in the adjoining villages without mass treatment. None in the two control groups suffered from the syndrome or any other encephalitis-like disease within the same period. Statistical tests for the differences between E and either N1 or N2 separately is highly significant. (between E and N1: P = 0.000553, P < 0.001; between E and N2: P = 0.000325, P < 0.001). The overall attributable risk (AR) is 45.8/100,000 and that for female is 93.8/100,000. However, the difference between the incidence rates of the disease in female and male is not statistically significant (P > 0.025). It is shown that LMS is obviously the causative factor of the disease.

[Epidemiological investigation on an outbreak of angiostrongyliasis cantonensis in Wenzhou].

OBJECTIVE: To find out the cause and transmission factors of an outbreak of eosinophilic meningoradiculitis in Wenzhou City during October to November in 1997. METHODS: In addition to a retrospective cohort study on 182 persons who had dined at a same restaurant of the city, etiological and immunoserological investigations were conducted. RESULTS: Among 105 cases who had eaten the undercooked Ampullaria gigas in that restaurant, 47 cases were infected, the incidence rate was 44.8%; whereas none of the persons who did not eat the under-cooked Ampullaria gigas in that restaurant got the infection, the difference between the two groups being significant(P < 0.001). The incidence rate of the cases who had eaten 4 and more pieces of the undercooked Ampullaria gigas was 86.2%(25/29), while that of those who had eaten less than 4 pieces was 28.9%(22/76), the difference between the two being very significant (chi 2 = 27.83, P < 0.001, RR = 2.98). The third stage larvae of the Angiostrongylus cantonensis were found out from Ampullaria gigas living in the same locality, and the adult worms of Angiostrongylus contonensis were found out from the rats living in the locality else. The positive rate of serum anti-Angiostrongylus cantonensis antibody in the patients was 84.0%. CONCLUSION: On the basis of the clinical, epidemiological, immunoserological and etiological investigations, an outbreak of the angiostrongyliasis cantonensis caused by eating undercooked Ampullaria gigas was confirmed.

Early-life exposure to lipopolysaccharide reduces the severity of experimental autoimmune encephalomyelitis in adulthood and correlated with increased urine corticosterone and apoptotic CD4+ T cells.

Early-life exposure to bacterial endotoxins, such as lipopolysaccharides (LPS), can provide neuroprotection against experimental autoimmune encephalomyelitis (EAE) during adulthood, possibly through altering the responsiveness of the immune system. Here, we show that exposure of LPS to neonatal rats resulted in a sustained elevation of corticosterone level in urine when compared with saline-treated rats, and that the high level of urine corticosterone was maintained during the progression of EAE (P<0.05). This high level of production of corticosterone plays an important role in altering the predisposition to EAE-induced neuroinflammation, as a positive correlation occurred between the concentration of urine corticosterone and the increased apoptotic CD4(+) T cells from the peripheral blood. LPS-treated rats also showed a reduced number of CD3(+) T cells in the spinal cord. The splenic antigen-presenting cells showed a reduced expression of MHC II during EAE development in LPS-exposed rats when compared with rats exposed to the saline-treated control. Together, these findings suggest that treating neonatal rats with LPS evokes a sustained elevation of glucocorticoid, which may suppress immune response during EAE by increasing apoptosis of CD4(+) T cells and reducing the expression of MHC II on antigen-presenting cells. Therefore, exposing neonates to bacterial endotoxin may further be developed as an immunization strategy to prevent human multiple sclerosis and other inflammatory brain diseases.