Evidences for diabetes and insulin mimetic activity of medicinal plants: Present status and future prospects.

Diabetes mellitus (DM) is a considerable systemic metabolic disorder to exhibit various metabolic and cardiovascular disorders, mainly hyperglycemia. The global projected estimate of diabetes in 2030 will be about 439 million adults, out of which 300 million expected are of type-2 diabetes mellitus (T2DM). The present knowledge revealed responsible factors, occurrence and mechanism of these factors involved in the DM diseases. Hence, the aim of this review is to address and summarize the causes, plant resources, importance, present status and future programmes for diabetes control. The present review answers the contemporary present questions raised in the scientific field on DM. Two major problems are explained in detail about the autoimmune attack or dysfunction of ß-cell and insulin resistance involved for Type 1 and Type 2 DM, respectively. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, many preferred herbal formulations due to lesser side effects and low cost. For this reason still it is getting increased attention in searching antidiabetic medicinal plants for hot research and to develop targeted medicine. Recurrence of islet autoimmunity lesson from pancreatic islet cell transplantation to cure T1D was outlined. With these highlights, the review summarizes the current knowledge on diabetes occurrence, factors (environmental and genetics), and types (I, II, gestation, and secondary DM), antidiabetic plants, sources for insulin mimetic plant principle compounds and their target mechanism with current and future trusted research areas for controlling of DM.

Synthesis of 4-Isoxazolines through Gold(I)-Catalyzed Cyclization of Propargylic N-Hydroxylamines.

New catalytic methods for the synthesis of 4-isoxazolines have been developed via catalytic intramolecular cyclizations of propargylic N-hydroxylamines. The reactions proceed rapidly in less than 1 h at room temperature in the presence of 5 mol % (PPh3)AuCl/5 mol % AgOTf or 5 mol % (PPh3)AuNTf2. This process features an efficient route to 4-isoxazolines with high yields, short reaction times, and mild reaction conditions.

Immunoreactivity and trypsin sensitivity of recombinant virus-like particles of foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is an important infection affecting the health and productivity of cloven-hoofed livestock. Development of improved vaccines and diagnostic reagents is being explored to facilitate the disease control. There is an emerging interest in virus-like particles (VLPs), as their constituent structural proteins are the major immunogens. The VLPs are similar to natural virus particles but lack viral nucleic acid. The objective of the present study was to express the VLPs of FMD virus (FMDV) serotype Asia-1 (IND 63/72), using baculovirus system and characterize them for antigenic structure. The VLPs expressed in insect cells showed immunoreactivity similar to inactivated cell culture FMDV. Further they possess similar sensitivity to trypsin as the inactivated cell culture FMDV, suggesting that trypsin-sensitive antigenic sites could be similarly arranged. Our findings suggest that the FMD VLPs have similar antigenic conformational feature like the wild type virus, thus supporting their utility in development of non-infectious FMD vaccines and/or diagnostic assays.

Hydrophobic interactions in donor-disulphide-acceptor (DSSA) probes looking beyond fluorescence resonance energy transfer theory.

Donor-linker-acceptor (DSSA) is a concept in fluorescence chemistry with acceptor being a fluorescent compound (FRET) or quencher. The DSSA probes used to measure thiol levels in vitro and in vivo. The reduction potential of these dyes are in the range of -0.60 V, much lower than the best thiol reductant reported in literature, the DTT (-0.33 V). DSSA disulphide having an unusually low reduction potential compared to the typical thiol reductants is a puzzle. Secondly, DSSA probes have a cyclized rhodamine ring as acceptor which does not have any spectral overlap with fluorescein, but quenches its absorbance and fluorescence. To understand the structural features of DSSA probes, we have synthesized DSSANa and DSSAOr. The calculated reduction potential of these dyes suggest that DSSA probes have an alternate mechanism from the FRET based quenching, namely hydrophobic interaction or dye to dye quenching. The standard reduction potential change with increasing complexity and steric hindrance of the molecule is small, suggesting that ultra- low Eo' has no contribution from the disulphide linker and is based on structural interactions between fluorescein and cyclized rhodamine. Our results help to understand the DSSA probe quenching mechanism and provide ways to design fluorescent probes.

A large-volume sputum dry storage and transportation device for molecular and culture-based diagnosis of tuberculosis.

Technologies for preservation of specimens in the absence of cold chains are essential for optimum utilization of existing laboratory services in the developing world. We present a prototype called specimen transportation tube (SPECTRA-tube) for the collection, exposure-free drying, ambient transportation, and liquid state recovery of large-volume (>1 mL) specimens. Specimens introduced into the SPECTRA-tube are dried in glass fiber membranes, which are critical for efficient liquid-state sample recovery by rehydration and centrifugation. SPECTRA-tube is demonstrated for the dry storage of sputum for tuberculosis detection. Mycobacterium smegmatis (Msm)-spiked mock sputum dried in a native Standard 17 glass fiber was stable for molecular testing after 10 day storage at 45 °C and for culture testing after 10- and 5-day storage at 37 °C and 45 °C, respectively. Compatibility with human sputum storage was demonstrated by dry storing 1.2 mL Mycobacterium bovis-spiked human sputum in a SPECTRA-tube for 5 days at room temperature. We have thus demonstrated the first workflow for dry storage of sputum followed by molecular and culture testing. Compared to existing specimen dry storage technologies, SPECTRA-tube significantly increases the volume of liquid specimens that can be transported in the dry state and enables the recovery of the entire sample in the liquid state, rendering it compatible with conventional downstream analysis methods.

Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines.

Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors. Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120. The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots. No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells. However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes.

Antibiotic resistance: A cross-sectional study on knowledge, attitude, and practices among veterinarians of Haryana state in India.

AIM: The current study aimed to assess the knowledge, attitude, and practices pertaining to antibiotic usage among the field veterinarians who serve as nodal officers playing a crucial role in disseminating knowledge to the farmers regarding livestock management practices in India. MATERIALS AND METHODS: A pilot study was conducted in which 106 of the 173 field veterinarians of Haryana, India, agreed to contribute through their valuable participation in the study. The collected data were critically analyzed by simple descriptive statistics, and the responses were ranked using Garrett's ranking method. RESULTS: Our study found that most of the clinicians were aware of the fundamental clinical aspects of antibiotic resistance (AR), i.e., the general causes and transmission of resistance, response during treatment failure, and safe disposal of hospital waste. Further, implementation of "antibiotic stewardship" (rational/responsible use of antibiotics) and interruption of AR transmission by means of cross-kingdom pathogens are two ways to restrict the spread of resistant pathogens which were not in the clinical purview of majority of the clinicians. This highlights a lack of awareness and scope of improving clinician's knowledge pertaining to AR. Moreover, we got to know the methodology adopted by farmers for disposal of infected milk from diseased udders as well as their attitude toward diseased and unproductive animals. CONCLUSION: This study provides snippets of the current animal husbandry practices prevalent at the field level which would assist to plug in the gaps of knowledge regarding AR among the veterinarians as well as the general public and serve to reduce its deleterious impacts in Indian animal farming as well as in the world through the concept of "One World, One Health."

A new method to generate an almost-diagonal matrix in the boundary integral equation formulation.

In this work, a new numerical procedure is developed to generate an almost-diagonal matrix for the solution of boundary integral equation formulation dealing with acoustic scattering problems. The major drawback of the traditional boundary integral equation procedure resulting in a dense system matrix is eliminated in this new procedure by grouping the basis functions into a cluster. The geometry of the structure is modeled by planar triangles and the basis functions are defined on the nodes. By doing so, one can get a benefit of a smaller size matrix to begin with. Furthermore, by grouping these node-based basis functions into a cluster, an almost-diagonal matrix is generated. Thus, the solution procedure developed in this work may be utilized for very large scattering problems since the required computer resources are very low. The solution procedure developed in this work is validated for the scattering cross section of the simple shapes with the closed form solutions wherever available and with the other numerical solution procedures.

Novel T-C@AgNPs mediated biocidal mechanism against biofilm associated methicillin-resistant Staphylococcus aureus (Bap-MRSA) 090, cytotoxicity and its molecular docking studies.

Staphylococcus aureus is a commonly found pathogen that can cause food-spoilage and life threatening infections. However, the potential molecular effects of natural active thymol molecules and chitosan silver nanoparticles (C@AgNPs) in bacteria remain unclear. This gap in the literature has prompted us to study the effects of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) against biofilm associated proteins in methicillin-resistant S. aureus (Bap-MRSA) 090 and also their toxicity, anti-cancer activity, and validation of their in silico molecular docking. The results showed excellent antibacterial activity of T-C@AgNPs against Bap-MRSA 090, having a minimum inhibitory concentration of 100 µg mL-1 and a 10.08 ± 0.06 mm zone of inhibition (ZOI). The cyclic voltammogram (CV) analysis clearly showed pore forming of T-C@AgNPs at 300 µg mL-1 concentration, and evidence of the interruption of the electron transport chain was clearly seen. The 200 µg mL-1 concentration exhibited a 52.60 ± 0.25% anti-biofilm property by T-C@AgNPs against Bap-MRSA 090. The T-C@AgNPs showed no toxicity to peripheral blood mononuclear cells (PBMC) (IC50 = 221 ± 0.71 µg mL-1) compared to the control, and anti-cancer activity against human triple negative breast cancer cell line (MDA-MB-231) (IC50 110 ± 1.0 µg mL-1) compared to the standard drug Doxorubicin (IC50 = 19 ± 1.0). The excellent properties of T-C@AgNPs were validated by in silico molecular docking studies and showed best match scoring to target proteins compared to standards. These excellent properties of T-C@AgNPs highlight for the first time its pharmacology and potential in medicinal drug development applications for future research.

On the possible mechanism of recognition of DNA base sequence by steroid hormones.

Geometry of the complex of a steroid hormone, dexamethasone, with a hexanucleotide sequence from the glucocorticoid responsive element d(TGTTCT)2, is optimised here using computer aided geometry simulation with an energy minimization technique. We have also optimised its geometries with genetically modified and arbitrarily chosen DNA sequences. The drug molecule is considered to have both intercalative as well as non-intercalative binding. Comparison of energetics and stereochemical aspects, as well as the H-bonding scheme, is used here to bring out salient features about the mechanism of DNA sequence recognition by steroid hormones.

CD4(81-92)-based peptide derivatives. Structural requirements for blockade of HIV infection, blockade of HIV-induced syncytium formation, and virostatic activity in vitro.

CD4(81-92) peptide block human immunodeficiency virus (HIV) infection, virus-induced cell fusion, and antigen production by HIV-1-infected cells when derivatized on specific amino acid residues. An extensive series of structural variants of 1,4,5-tribenzyl-10-acetyl-CD4(81-92) were tested as anti-viral agents in an attempt to define the sequence and derivatization requirements for antiviral activity, and to maximize potency and stability for use as potential therapeutic agents. Alteration of the primary amino acid sequence of the stem compound 1,4,5-tribenzyl-CD4(81-92) diminished or abolished in parallel all three indices of anti-viral activity in a series of altered sequence compounds. Replacement of d- for l-amino acid residues at positions 1, 2, 3, 4, 5, or 6 but not position 10 decreased anti-viral potency, again with parallel effects on infection, synctium formation, and virostatic activity. Omission of the glutamine residue at position 9 did not affect anti-viral potency, while removal of the glutamic acids at position 11 and 12 resulted in virtually complete loss of biological activity. Changes in the derivatization pattern of the CD4(81-92) peptide backbone also affected anti-viral potency and efficacy. Optimal activity was obtained with benzyl residues at positions 1, 4, and 5, whereas the 1,4,7-tribenzyl-CD4(81-92) compound was without activity in all assays tested. Replacement of one of the benzyl groups with an acetamidomethyl moiety resulted in complete loss of biological activity. The previously reported (Nara et al., Proc Natl Acad Sci USA 86: 7139-7143, 1989) virostatic activity of 1,4,5-tribenzyl-10-acetyl-CD4(81-92) (peptide #18) is apparently due to acetylation, since the desacetyl stem compound shows much less virostatic activity while still possessing full anti-infective and anti-syncytial activity, and acetylation of the N-terminus rather than the lysine of 1,4,5-tribenzyl-CD4(81-92) yields a virostatic compound equipotent to peptide #18. Cyclization of the tribenzyl peptide to further conformationally restrict the molecule resulted in a compound with anti-infection, anti-syncytial, and virostatic activity at submicromolar concentrations.

Surgical treatment of complications 45 years after extraperiosteal pneumonolysis and plombage using acrylic resin balls for cavitary pulmonary tuberculosis.

An infected axillary sinus tract discharged balls made of an acrylic resin consisting essentially of polymerized methyl methacrylate (Lucite) 45 years following performance of an extraperiosteal pneumonolysis and Lucite ball plombage for collapse therapy of right upper lobe cavitary tuberculosis. Surgical extraction of the balls was performed, followed by a partial decortication of the lung and intrathoracic transposition of a pectoralis major muscle flap to fill the residual pleural space. Primary healing was attained, and the patient is well 1 1/2 years after surgery.

Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction.

From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival.

Inhibitory cyclic analogues and chlorambucil derivatives of bombesin-like peptides.

Analogues of the amphibian neuropeptide, bombesin, and of the mammalian homologue, gastrin-releasing peptide, have been synthesized and their biological activity studied in small cell lung carcinoma and rat pancreatic acinar cells. The compounds are truncated sequences of the active tetradecapeptide BN(1-14) or GRP(20-27). Peptides were cyclized between position 5 or 7 and the carboxyl end of the des-Met14 fragment with D and L Ala11 and Lys5 substitutions, as well as various N-terminal groups attached. The smallest cyclic peptide, BN(7-13), bound to SCLC membranes with microM potency and inhibited BN stimulation of intracellular Ca++ levels. The most potent inhibitor is N-chloroambucil-[His7,D-Ala11]BN(7-13)ethyl ester, which antagonized BN function in SCLC and acinar cells with nM potency and also inhibited clonal growth of carcinoma cell lines.

A novel nonphagocytic mechanism of erythrocyte destruction involving direct cell-mediated cytotoxicity.

The number of erythrocytes fell when co-cultured with cell preparations derived from mouse spleen, thymus, bone marrow, or peritoneal exudate (PE) cells. Erythrocyte-depletion activities (EDA) of different leukocyte preparations were in the order PE > spleen > thymus > bone marrow. Adherent, nonadherent, T-depleted, and T-enriched cell subpopulations had comparable EDA. Spleen cells from athymic nude mice, however, lacked significant EDA. In addition, EDA was boosted by Concanavalin A (Con A) but not by lipopolysaccharide, indicating that T cells may play a crucial role in inducing EDA in spleen cells. Paraformaldehyde-fixed spleen or PE cells, as well as membrane preparations isolated from spleen cells, efficiently lysed erythrocytes. Erythrocyte ghost membranes inhibited erythrocyte lysis by control or paraformaldehyde-fixed spleen cells. Treatment with hamster anti-mouse Fas or anti-mouse tumor necrosis factor receptor (TNFR) antibody could opsonize erythrocytes for faster depletion by spleen cells, suggesting an expression of Fas and TNFR on erythrocytes. TNF alpha could lyse erythrocytes in a dose-dependent fashion. Additionally, enhanced spleen cell EDA induced in response to succenyl Con-A could be blocked by anti-TNF alpha antibodies. Our results provide evidence for a direct cell-mediated cytotoxicity (CMC) of erythrocytes by leukocytes. A role of molecules of Fas and the TNF family in CMC of erythrocytes has also been suggested. Further work is needed to understand if, and to what extent, CMC of erythrocytes contributes to erythrocyte destruction in vivo and to determine its patho-physiological significance.

Parascapular free flaps for head and neck reconstruction.

We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck.

Coverage strategies in total joint replacement.

The strategy for soft-tissue management following total joint arthroplasty begins with prevention. The medical status of the patient is optimized preoperatively. Meticulous surgical technique with liberalized indication for flap closure primarily will reduce soft-tissue failures. Early identification and aggressive team management of complications are critical to decrease long-term morbidity and to obtain a good functional result.

The pinwheel flap nipple and barrier areola graft reconstruction.

The pinwheel flap with a snug barrier areola graft appears to be an efficacious modification of Little's quadripod flap for nipple reconstruction. Further, long-term evaluation is needed to test the validity of these observations over several years.

Clinical applications of the extended deep inferior epigastric flap.

The extended deep inferior epigastric flap, described by Taylor et al. in 1983, consists of the lower portion of the rectus abdominis muscle and a superolateral fasciocutaneous extension based on the periumbilical perforators. We have used this flap four times to close large defects of the abdomen, groin, and thigh and twice as a free flap to close wounds of the head and leg. There were no ischemic complications, and there was uncomplicated wound healing in the recipient and in the donor wounds. We recommend this highly versatile and reliable flap as one to be considered early in planning the closure of large wounds.