Calcium dobesilate ameliorates lung injury following lower limb ischemia/reperfusion

We examined the effects of calcium dobesilate on ameliorating the lung damage following ischemia-reperfusion injury in skeletal muscle of rats. A well known antioxidant, dimethyl sulfoxide, was also tested for comparison. The study included three groups: normal saline, dimethyl sulfoxide and calcium dobesilate. Plasma bicarbonate, creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS), as well as muscle and lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. The dimethyl sulfoxide group showed significant amelioration of plasma (p = 0.004), skeletal muscle (p = 0.006) and lung TBARS (p = 0.004) levels, compared with controls. Calcium dobesilate-treated rats showed significantly low level muscle (p = 0.025) and lung TBARS (p = 0.004), compared with the control group. The extent of lung injury according to the histological findings was less in the dimethyl sulfoxide (p = 0.004) and calcium dobesilate (p = 0.003) groups. These observations indicated that calcium dobesilate acted effectively in the prevention of lung damage following ischemia-reperfusion injury in the rat skeletal muscle.     

Anticarcinogenic Effects of the Ethanolic Extract of Salix aegyptiaca in Colon Cancer Cells: Involvement of Akt/PKB and MAPK Pathways

The bark from Salix species of plants has been traditionally consumed for its antiinflammatory properties. Because inflammation frequently accompanies the progress of colorectal cancer (CRC), we have evaluated the anticancer properties of the ethanolic extract from the bark (EEB) of S. aegyptiaca, a Salix species endogenous to the Middle East, using HCT-116 and HT29 CRC cell lines. Fresh bark from S. aegyptiaca was extracted with ethanol, fractionated by solvent-solvent partitioning and the fractions were analyzed by tandem mass spectrometry. Catechin, catechol, and salicin were the most abundant constituents of the extract. Interestingly, EEB showed the highest anticancer effect in the colon cancer cells followed by its fractions in ethyl acetate and water, with catechin, catechol, and salicin showing the least efficacy. EEB could strongly reduce the proliferation of the cancer cells, but not of CCD-18Co, normal colon fibroblast cell line. Accompanying this was cell cycle arrest at G1/S independent of DNA damage in the cancer cells, induction of apoptosis through a p53 dependent pathway and an inhibition of PI3K/Akt and MAP Kinase pathways at levels comparable to known commercial inhibitors. We propose that the combination of the polyphenols and flavonoids in EEB contributes toward its potent anticarcinogenic effects.

[Supplementary materials are available for this article. Go to the publisher's online edition of Nutrition and Cancer for the following free supplemental resource(s): Supplementary Figure 1 and Supplementary Figure 2.]     

Vagus nerve afferent and efferent innervation of the rat uterus: An electrophysiological and HRP study

To determine a possible brainstem connection with the uterus, a study with electrophysiological techniques and horseradish peroxidase (HRP) tracing was performed in the rat. Neurons of the nucleus of the tractus solitarius decreased in discharge frequency during cervicovaginal distension. HRP injections into the uterine walls resulted in the appearance of labelled cells in the nodose ganglion and in the dorsal motor nucleus of the vagus nerve. The results demonstrate a direct bidirectional vagal complex-uterus connection via the vagus nerve. Results are discussed in terms of a complex uterus control system in which the paraventricular nucleus might play an integrative role.     

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency

Journal of Clinical Immunology - NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are...     

Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide

Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as immune adjuvants, antiallergens, anticancer, and immunoprotective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes that both types of ODN bind to and are internalized by the same individual B cells, NK cells, and monocytes. However, the intracellular localization of "D" and "K" ODN differs, as does their functional activity: "K" type ODN trigger monocytes and B cells to proliferate and secrete IL-6 and IgM, whereas "D" type ODN induce NK cells to produce IFN-gamma and monocytes to differentiate into CD83(+)/CD86(+) dendritic cells. In monocytes, these two types of ODN (which differ in backbone composition and CpG motif) cross-inhibit one another's activity. Thus, different types of CpG ODN have distinct and in some cases incompatible effects on the same cells, a finding with important implications for the therapeutic use of these agents.     

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study

AimSystemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics.Material and MethodAmong the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded.ResultsIn total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up.ConclusionsSLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.     

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.