Phosphorylated ganciclovir derivatives: design,synthesis and in vitro and in vivo immunomodulatory activity

Synthesis of a series of novel phosphorylated ganciclovir derivatives with bioactive amines/aminoacid esters as substituents was accomplished. These compounds were structurally characterized by IR, NMR (¹H, ¹³C, ³¹P), mass spectra and CHN analysis. The compounds (5a–m) have been evaluated for its in vitro and in vivo immunomodulatory activities. The amino acid ester-substituted ganciclovir derivatives, especially the 5g and 5i, increased the intracellular killing activity of the stimulated neutrophils. The in vivo experiment results show that the administration of compounds 5g and 5i (8 mg/kg body weight) to diet-induced immune impaired obese rats ameliorated the significant increase in immune cell counts (lymphocytes, neutrophils and monocytes). In addition, TNF-α, IL-6 and IL-1 secretions were considerably restored to normal by the compounds 5g and 5i with regulation in the release of C-reactive protein suggesting their potentiating effect on immune system dysfunction. These in vitro and in vivo results suggest that the phosphorylated ganciclovir derivatives 5g and 5i are strong immunomodulators.     

Effects of preoperative other diseases on the complications of senile cervical Tertebral operation in perioperative period

AIM: To investigate the effects of preoperative other diseases on the complications of senile cervical vertebral operation in perioperative period METHODS: 800 senile cervical vertebral cases were divided into two group: group A included the cases without other comorbidilies, and group B included the cases with hypertension, diabetes mellitus, coronary heart disease (CHD) or chronic obstructive pulmonary disease(COPD) . We retrospectively analyzed the changes of BP, oxygen saturation (Sad) and the incidence of cardiac arrhythmia during operation of group A and B. RESULTS: In perioperative period, the incidence of BP reduction or rising and cardiac arrhythmia in group B was more than that of group A. Incidence of SaO2 decreasing increases apparently in each stage and incidence of cerebrovascular, pulmonary complications and asphyxia led by incision bleeding increases apparently. CONCLUSION: The hypertension, CHD, diabetes mellitus and COPD were the main reasons of complications of the heart, the cerebral     

Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats

We examined the potential protective effect of BDNF against beta-amyloid-induced neurotoxicity in vitro and in vivo in rats. In neuronal cultures, BDNF had specific and dose-response protective effects on neuronal toxicity induced by Abeta(1-42) and Abeta(25-35). It completely reversed the toxic action induced by Abeta(1-42) and partially that induced by Abeta(25-35). These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB.FL) were localized in vitro in cortical neurons (mRNA and protein). In in vivo experiments, Abeta(25-35) was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Abeta(25-35)/BDNF interactions, i.e. local measurement of BDNF release, number of hippocampal hilar cells expressing SRIH mRNA and assessment of the corpus callosum damage (morphological examination, pyknotic nuclei counting and axon labeling with anti-MBP antibody). We conclude that BDNF possesses neuroprotective properties against toxic effects of Abeta peptides.     

Imaging features of common and uncommon bladder neoplasms

In this article, the authors discuss imaging features of common and less-common epithelial and nonepithelial bladder neoplasms. Epithelial tumors include entities, such as urothelial cell carcinoma, squamous cell carcinoma, and adenocarcinoma, along with less-common entities, such as small cell and carcinoid tumors. Nonepithelial or mesenchymal tumors are also less commonly encountered and include benign entities, such as leiomyoma and neurofibroma, and malignant entities, including leiomyosarcoma and lymphoma. Their imaging features with an emphasis on computed tomography and magnetic resonance imaging are described.     

PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D₂ (PGD₂) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD₂ and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine–mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD₂–CRTH2 pathway negatively regulates the Type 2 cytokine–driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.     

Effect of oral tobacco use and smoking on outcomes of Crohn's disease in India

Background and Aim

Smoking has been linked with adverse outcomes in Crohn's disease (CD); however, it is not known whether oral tobacco (OT) use affects disease outcomes in these patients. The study aimed to assess the association between smoking or OT and outcomes in CD.

Methods

Retrospective analysis was performed on prospectively maintained records of CD patients from 2004 to 2016. The parameters assessed included disease characteristics at baseline (location, behavior, age at onset, perianal disease, and extraintestinal manifestations), course pattern, and outcomes (surgery, hospitalizations, immunomodulator or biologics use, and steroid requirement).

Results

A total of 426 patients were included (mean age: 39.9 years; 59.9% men; median follow up: 71 months). Forty patients were ever‐OT users, and 59 were ever‐smokers, ever‐use being defined as daily use for at least 2 years. OT use was associated with male sex and smoking. Both OT use and smoking had no effect on baseline characteristics, but upper gastrointestinal disease was less common in ever‐smokers. Both OT use and smoking did not have any effect on surgery, immunomodulator, and biologic use. Similarly, no association was found between these outcomes and duration, daily, and cumulative exposure to tobacco. Current but not former tobacco use in both smoked (adjusted odds ratio = 2.59 [1.22–5.49]) and OT (adjusted odds ratio = 2.97 [1.03–8.6]) forms increased risk of hospitalizations.

Conclusion

Oral tobacco use and smoking had no significant detrimental effect on disease phenotype or medical and surgical requirements in CD in Indian patients, affirming other non‐Caucasian studies that found lack of effect of smoking. However, current tobacco use in any form was associated with hospitalization during follow up.     

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized,open-label,parallel-group,dose-ranging study

Clinical Rheumatology - The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to...