Circulating Gut-Homing (α4ß7+) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea.

Developing countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens, pan-Shigella surface protein antigen 1 (PSSP1) and PSSP2, common to all virulent Shigella strains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (α4ß7 (+)) antibody-secreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzyme-linked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive for Shigella infection by microbiological and real-time PCR assays, respectively. The frequency of α4ß7 (+) IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of the Shigella serotype isolated from these patients. Thus, α4ß7 (+) ASC responses to Ipas may be considered an indirect marker of Shigella infection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross-protection induced by natural Shigella infection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude.

Stereoselective synthesis of the macrolactone core of (+)-neopeltolide.

A stereoselective synthesis of the macrolactone core of the potent anticancer agent neopeltolide is disclosed. The key steps of the synthesis include asymmetric allylation using Krische' protocol, conjugate reduction using MacMillan's methodology, and an asymmetric hetero-Diels-Alder reaction using Jacobsen's catalyst. Substrate controlled diastereoselective 1,3-anti reduction of a keto alcohol, Luche reduction followed by Ireland-Claisen rearrangement, oxymercuration, and reductive lithiation are other key steps.

Effect of extract of Withania Somnifera on dehydration-induced oxidative stress-related uremia in male rats.

Dehydration or water deprivation in the body decreases urinary excretion and allows urea and other protein waste products to accumulate in the blood. The aim of the present study is to evaluate the association of uremia and oxidative stress by applying the herbal plant Withania somnifera (W. somnifera) (Aswagandha). The study was performed on male Wister strain rats in which, dehydration was achieved by water withdrawal. A total of 18 rats were studied and were randomly divided into three Groups: Group-1, control, Group-2, only dehydration and Group-3, dehydration + administration of aqueous root extract of W. somnifera, orally (50 mg/100 gm body weight/day) for 25 days. After 25 days of treatment, it was observed that the body weight of Group-3 animals had increased significantly, while that in Group-2 had decreased significantly. The liver enzymes in both blood and kidneys did not show any significant change in the three groups implying absence of any toxicity of the root extract. In Group-2 animals, the serum urea and creatinine levels increased sig-nificantly when compared with animals in Groups-1 and 3. The low levels of serum urea and crea-tinine in Group-3 animals indicates the protective effect of the plant extract against renal injury caused by dehydration. Dehydration-induced oxidative stress was established in our study by noting the low activities of super-oxide dismutase and catalase, both important antioxidant enzymes, in Group-2 animals; both enzymes were stabilized in animals of Groups-3 and 1. In conclusion, it is hypothesized that there is an antioxidative role of W. somnifera resulting in reducing the extent of renal injury as a result of oxidative stress.