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Biomedical subjects

V S Chauhan

Publications and source records attributed to V S Chauhan.

At least 19 recordsLinked to original sources
PubMed2006

Stabilization of unusual structures in peptides using alpha,beta-dehydrophenylalanine: crystal and solution structures of Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe.

The structures of two dehydropentapeptides, Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe (I) and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe (II) (Boc: t-butoxycarbonyl), have been determined by nuclear magnetic resonance (NMR), circular dichroism (CD), and X-ray crystallographic studies. The peptide I assumes a S-shaped flat beta-bend structure, characterized by two partially overlapping type II beta-bends and absence of a second 1 <-- 4 (N4--H . . . O1') intramolecular hydrogen bond. This is in contrast to the generally observed 3(10)-helical conformation in peptides with DeltaPhe at alternate positions. This report describes the novel conformation assumed by peptide I and compares it with that of the conserved tip of the V3 loop of the HIV-1 envelope glycoprotein gp120 (sequence, G:P319 to F:P324, PDB code 1ACY). The tip of the V3 loop also assumes a S-shaped conformation with Arg:P322, making an intramolecular side-chain-backbone interaction with the carbonyl oxygen of Gly:P319. Interestingly, in peptide I, C(gamma)HVal(3) makes a similar side-chain-backbone C--H . . . O hydrogen bond with the carbonyl oxygen of the Boc group. The observed overall similarity indicates the possible use of the peptide as a viral antagonist or synthetic antigen. Peptide II adopts a unique turn followed by a 3(10)-helix. Both peptides I and II are classical examples of stabilization of unusual structures in oligopeptides.

Amino Acid Sequence↗
PubMed2006

Immune responses to asexual blood-stages of malaria parasites.

The blood stage of the malaria parasite's life cycle is responsible for all the clinical symptoms of malaria. The development of clinical disease is dependent on the interplay of the infecting parasite with the immune status and genetic background of the host. Following repeated exposure to malaria parasites, individuals residing in endemic areas develop immunity. Naturally acquired immunity provides protection against clinical disease, especially severe malaria and death from malaria, although sterilizing immunity is never achieved. Given the absence of antigen processing in erythrocytes, immunity to blood stage malaria parasites is primarily conferred by humoral immune responses. Cellular and innate immune responses play a role in controlling parasite growth but may also contribute to malaria pathology. Here, we analyze the natural humoral immune responses acquired by individuals residing in P. falciparum endemic areas and review their role in providing protection against malaria. In addition, we review the dual potential of cellular and innate immune responses to control parasite multiplication and promote pathology.

Animals↗
PubMed2005

Incisional hernia--comparison of mesh repair with Cardiff repair: an university hospital experience.

BACKGROUND: Incisional hernia is a frequent complication of abdominal surgery. Various types of repair are recommended for incisional hernia. Suture and mesh repair are compared in the present study. METHOD: One hundred seventy one patients with incisional hernia underwent Cardiff repair (far and near sutures with reinforcement sutures) which was used as an open suture repair while onlay polypropylene mesh was used in the mesh repair technique. RESULT: Cardiff repair was performed in 116 patients with no mortality with recurrence in two patients with mean follow up of 7.1 years. Both these patients with recurrence had a defect measuring more than 10 cm in width. Mesh repair was carried out in 55 patients with no recurrence in mean follow up of 37 months. Seroma formation was noted in 7 (12.72%) with mesh repair as compared to 4 (3.44%) patients with Cardiff repair. CONCLUSION: We recommend Cardiff repair for primary and small to medium size incisional hernias. Onlay polypropylene mesh is ideal for tension-free hernia repair, recurrent incisional hernia and hernia defects wider than 10 cm.

Abdominal Wall↗
PubMed2005

Cyclo(L-leucyl-alpha,beta-dehydrophenylalanine): the first diketopiperazine containing an alpha,beta-dehydrophenylalanine residue.

The title compound (systematic name: 3-benzylidene-6-isobutylpiperazine-2,5-dione), C15H18N2O2, an alpha,beta-dehydrophenylalanine containing diketopiperazine, crystallizes in the space group P1 with two molecules in the asymmetric unit arranged antiparallel to one another. The alpha,beta-dehydrophenylalanine (DeltaPhe) residue in this cyclic peptide retains its planarity but deviates from the standard conformations observed in its linear analogues. Each type of molecule forms a linear chain with molecules of the same type via pairwise N-H...O hydrogen bonds, while weaker C-H...O interactions link the chains together to form a three-dimensional network.

Journal Article↗
PubMed2005

A Meccano set approach of joining trpzip a water soluble beta-hairpin peptide with a didehydrophenylalanine containing hydrophobic helical peptide.

A 16 residues long, water soluble, monomeric beta-hairpin peptide 'trpzip', stabilized by tryptophan zipper has been linked via a tetraglycyl linker to a hydrophobic didehydrophenylalnine (DeltaF) containing helical octapeptide. Circular dichroism studies of this 28 residues long peptide, 'trpzipalpha' (Ac-GEWTWDDATKTWTWTE-GGGG-DeltaFALDeltaFALDeltaFA-NH(2)) in water have revealed the presence of both the beta-hairpin and the helical conformations. This is the first instance where a DeltaF containing peptide has been found to display a helical fold in water. The fluorescence emission wavelengths of tryptophan in Ac-G-W-G-NH(2), trpzip and trpzipalpha were 341.5, 332.8 and 332.6 nm, respectively. The fluorescence quantum yield of trpzip was 2.6-fold higher than trpzipalpha suggesting that proximal interactions between the beta-hairpin and the helix caused the quenching of tryptophan fluorescence in the former by the DeltaFs in the latter. The molar ellipticity of the far UV couplet characteristic of trpzip was reduced in trpzipalpha and the CD based thermal melting temperatures at 228 nm were 62 degrees C (trpzip) and 57 degrees C (trpzipalpha). A concentration-dependent variable temperature CD study in water showed that in trpzipalpha, increasing temperature is detrimental to the beta-hairpin, but it augments the helical motif, perhaps by intermolecular oligomerization. Our results show that in water, trpzipalpha exhibits long-range interactions between two different secondary structures. In contrast to trpzip, trpzipalpha has shown a greater tendency to oligomerize in water.

Amino Acid Sequence↗
PubMed2005

The prevalence of pressure ulcers in hospitalised patients in a university hospital in India.

OBJECTIVE: To estimate the prevalence of pressure ulcers in hospitalised patients and any underlying or predisposing factors to ulceration. METHOD: This cross-sectional study took place in a university hospital in Varanasi, India. A total of 445 patients hospitalised in medical and surgical wards were examined in a single day for the number, site and grade of pressure ulcers. Haemoglobin, serum albumin and blood sugar levels of patients with pressure ulcers were recorded. RESULTS: The prevalence of pressure ulcers was high (4.94%). Anaemia, malnutrition and diabetes were important risk factors, while morbidity due to pressure ulcers in long-stay wards, such as neurology, was exceptionally high (40.9%). CONCLUSION: Pressure ulcers remain one of the most neglected aspects of health-care provision in India and identifying their associated risk factors at an early stage may go a long way in preventing their occurrence.

Adult↗
PubMed2004

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures.

Amino Acid Sequence↗
PubMed2004

Enteric perforation--single-layer closure.

A hundred cases of enteric perforation, treated surgically by single- or double-layer closure, were studied prospectively. Mortality and morbidity rates were 10-18 and 37-42% and comparable in the two groups. The presence of preoperative shock was the single most important prognostic indicator observed in this study. Hence it is good closure of the perforation rather than single- or double-layer closure that determines the outcome in patients with enteric perforation.

Adolescent↗
PubMed2004

Comparison of immunogenicities of recombinant Plasmodium vivax merozoite surface protein 1 19- and 42-kiloDalton fragments expressed in Escherichia coli.

The 42- and 19-kDa C-terminal fragments of merozoite surface protein 1 (MSP-1(42) and MSP-1(19), respectively) are both promising blood-stage vaccine candidate antigens. At present, it is not clear which of the two antigens will be more suitable for inclusion in a cocktail malaria vaccine. In the present study, we expressed the two C-terminal fragments of Plasmodium vivax MSP-1 (PvMSP-1) in an Escherichia coli expression system and purified them by using a rapid two-step protocol. Both of the products were recognized by monoclonal antibodies against PvMSP-1 as well as by immune sera from several individuals exposed to P. vivax. We analyzed and compared the immunological responses to recombinant PvMSP-1(19) and PvMSP-1(42) in mice by using six different adjuvant formulations. Moderate to high antibody responses were observed with both of the antigens in different adjuvant formulations. Surprisingly, alum, which is generally considered to be a poor adjuvant for recombinant malaria antigens, was found to be as good an adjuvant as Montanide ISA 720, ASO2A, and other adjuvant formulations. Most adjuvant formulations induced high levels of immunoglobulin G1 (IgG1), followed by IgG3 and IgG2. Lymphocytes from animals in the PvMSP-1(42)- and PvMSP-1(19)-immunized groups showed proliferative responses upon stimulation with the respective antigens, and high levels of interleukin-4 (IL-4), IL-5, and gamma interferon were detected in the culture supernatants. Immunodepletion studies with sera from mice immunized with these two antigens showed that while immunization with PvMSP-1(42) does produce a PvMSP-1(19)-specific response, a substantial portion is also focused on structures in PvMSP-1(42) not represented by the epidermal growth factor-like domains of PvMSP-1(19). These findings may have implications for the design of MSP-1-based vaccine constructs.

Adjuvants, Immunologic↗
PubMed2003

Role of a two-residue spacer in an alpha,beta-Didehydrophenylalanine containing hexapeptide: crystal and solution structure of Boc-val-deltaPhe-Leu-Ala-deltaPhe-Ala-OMe.

The peptide Boc-Val1-deltaPhe2-Leu3-Ala4-deltaPhe5-Ala6-OMe has been examined for the structural consequence of placing a two-residue segment between the deltaPhe residues. The peptide is stabilized by four consecutive beta-turns. The overall conformation of the molecule is a right-handed 3(10)-helix, with average (phi, psi) values (-67.7 degrees, -22.7 degrees), unwound at the C-terminus. The 1H NMR results also suggest that the peptide maintains its 3(10)-helical structure in solution as observed in the crystal state. The crystal structure is stabilized through head-to-tail hydrogen bonds and a repertoire of aromatic interactions laterally directed between adjacent helices, which are antiparallel to each other. The aromatic ring of deltaPhe5 forms the hub of multicentred interactions, namely as a donor in aromatic C-H...pi and aromatic C-H...O=C interactions and as an acceptor in a CH3...pi interaction. The present structure uniquely illustrates the unusual capability of a deltaPhe ring to host such concerted interactions and suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures.

Circular Dichroism↗
PubMed2003

Nonhealing wounds--a therapeutic dilemma.

Chronic wounds of the lower extremity are a therapeutic dilemma. In India, chronic wounds are caused by factors other than impaired circulation and diabetes, which account for most of this clinical problem in Western societies. A study of 2 topical agents, placental extract and phenytoin powder, is presented in this paper. One hundred fifty patients were randomly assigned to these treatments or to saline dressings (control). It was observed that patients receiving active topical treatments responded better than those in the control group. The importance of this finding should be viewed with the perspective that these topical treatments are inexpensive and easily available in India. The study also piloted measurements of angiogenic responses in 1 group, and the findings encourage further exploration with the technique and topical agent.

Journal Article↗
PubMed2003

Management of plantar ulcers in Hansen's disease.

Plantar ulcers occur in patients with Hansen's disease not because of the disease but because of its neuropathic effects on the skin over the feet. This enhances the risk of trauma to patients' feet, leading to the development of ulcers. This short article reviews the current management of leprosy on the basis of World Health Organization guidelines and the complexities of plantar ulceration in such patients. A guide to its management and prevention is also discussed.

Journal Article↗
PubMed2002

Development of molecular markers for screening of Alnus nepalensis (D. Don) genotypes for the nitrogenase activity of actinorhizal root nodules.

Alnus nepalensis (D. Don), an alder species, is an actinorhizal tree found in the hilly regions of Eastern and Northeastern India. It is useful in the reclamation of wastelands generated by land slips, shifting agriculture and coal mining. To maximise the soil regeneration capacity of alder plantations, it would be useful to be able to select superior alder genotypes at the nursery level. Conventional methods of genotype screening are difficult to apply to open-pollinated forest trees. It would be beneficial if molecular markers could be developed for early screening. The study reported here was conducted to assess the feasibility of developing PCR-based AFLP and RFLP screening tools for the selection of superior genotypes of this valuable tree with respect to their ability to support efficient nitrogen-fixing root nodules. It was found that a multi-site strategy, including the chloroplast rrn operon and the nuclear rRNA genes, yielded promising results. A molecular marker for genotypes that support nodules with low nitrogenase activity was also identified.

Alnus↗
PubMed2002

Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization.

A lack of molecular understanding of the targets and mechanisms of artemisinin action has impeded the improvisation of more efficient antimalarials based on this class of endoperoxide drugs. We have synthesized a heme-artemisinin adduct designated as "hemart" to discover if it mediates the ability of artemisinin to inhibit heme polymerization. Hemart mimics heme in binding to Plasmodium falciparum histidine-rich protein II (PfHRP II) but cannot self-polymerize. Instead, it inhibits all heme polymerizations, including basal and those triggered by PfHRP II, Monooleoyl glycerol (MOG), or P. yoelii extract. Hemart has an edge over heme in displacing heme from PfHRP II, and either low pH or chloroquine dissociates heme but not hemart from PfHRP II. Our results suggest that hemart, by mimicking heme, stalls all mechanisms of heme polymerization, resulting in the death of the malaria parasite.

Animals↗