219 research outputs found
UvA-DARE (Digital Academic Repository) Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events-Results from the INFIR Cohort Study
No full textPredicting neuropathy and reactions in leprosy at diagnosis and before incident eventsResults from the INFIR Cohort Study Smith, W.C.S.; Nicholls, P.G.; Das, L.; Barkataki, P.; Suneetha, S.; Suneetha, L.; Jadhav, R.; Rao, P.S.S.S.; Wilder-Smith, E.P.; Lockwood, D.N.J.; van Brakel, W.H. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible
Predicting neuropathy and reactions in leprosy at diagnosis and before incident events. Results from the INFIR cohort study
No full textBackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability
The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India
No full textThe aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as ‘gold standard’ for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, there impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed in indicate more serve neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk for those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment
Real‐Time VCC Monitoring and Forecasting in HEK‐Cell‐Based rAAV Vector Production Using Capacitance Spectroscopy
No full textABSTRACT Recombinant adeno‐associated virus (rAAV) vector production is a complex process in which the robust cultivation of human embryonic kidney cells (HEK293) plays a critical role in generating high‐quality viral vectors. Tracking the viable cell concentration (VCC) during upstream production is essential for process monitoring and for implementing actions that ensure optimal process management. The advent of inline capacitance probes has introduced a crucial process analytical technology (PAT) tool for real‐time VCC measurement. Here, we present the development and application of a method for real‐time monitoring of VCC in HEK293‐based rAAV vector production. In a first step, BioPAT Viamass probes were used to record capacitance data of individual 10 L rAAV‐8 batches within a frequency range of 50 kHz–20 MHz. Based on the capacitance data, a linear single‐frequency model and an orthogonal partial least square (OPLS) multifrequency model for VCC prediction were developed. Subsequently, these models were deployed inline, and predictions were exposed into BioPAT MFCS bioprocess control software, enabling real‐time VCC monitoring in subsequent rAAV‐8 production batches. In addition, the continuous VCC signal was used as input for an exponential cell growth model that was deployed inline to provide accurate real‐time forecasting of the transfection time point. To the best of our knowledge, this is the first example of inline deployment of VCC and Time‐Till‐Transfection predictive models to the bioprocess control system for real‐time monitoring and forecasting of these parameters in HEK‐cell‐based transient rAAV vector production
Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
No full textBACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R
Comparative Studies on Antimicrobial and Antifungal Efficacy from Bixa Orellana L., Lantana Camara L., Stachytarpheta Jamaicensis (l.)vahl., Hyptis Suaveolens (l.) Poit.with Triclosan
No full textThe aim of the present study was to assess the Antimicrobial and Antifungal activities of the Phenolic leaf extracts of Bixa orellana L., Lantana camara L and Stachytarpheta jamaicensis (L.) Vahl. Hyptis
suaveolens (L.) Piot. and the Triclosan, a chlorinated aromatic compound with antibacterial and antifungal properties used in common house hold and personal care products and to compare household
and personal care products and to compare their effectiveness against 4 bacterial strains - 2 Gram Positive
strains – Staphylococcus aurens and Bacillus substitis and 2 Gram negative strains – Escherischia coli
and Pseudomonas fluorescens and 3 Fungi- Aspergillus niger, Aspergillus flavus and Mucor Sp., by Agar
well diffusion Assay. The phenolic extracts of all the 4 plants showed Maximum (80-100%), Relative
inhibition against Pseudomonas fluorescence, Moderate inhibition (30-70%) against Staphylococcus
aurens and Bacillus substilis and least inhibition (30-47%) against Escherischia coli, while, the
Antifungal efficacy of all the 4 Phenolic plant extracts were observed to be effective at the concentration
ranging from 70-300 µg. The plant phenolic extracts for Antimicrobial and Antifungal properties were
compared with Standard Triclosan, a chlorinated compound. Our studies showed that the phenolic
components of plant origin for antibacterial activity were equivalent to Triclosan with the same
concentration, while for antifungal activity slightly higher concentrations could be a better alternative and
hence there could be a substitution for Triclosan by Plant Phenolic Extracts used in house hold and
personal care products, in future days to come
Spectral, nonlinear optical and optical limiting properties of l-phenylalanine l-phenylalaninium formate single crystal
No full textSimulating the impact of climate change and adaptation strategies on farm productivity and income: A bioeconomic analysis
No full textThis study applied at the farm level in Tunisia aims at understanding the effects of climate change on agricultural productivity and income in Africa. Possible future climates are presented through different climate scenarios. The latter combines three levels of increasing temperature (1�centigrade (C), 2�C, and 3�C) with two levels of decreasing precipitation (10 and 20 percent) and a doubling of carbon dioxide concentration in the atmosphere (350 to 700 parts per million). The farming system of production is replicated through a bioeconomic model; that is, one that couples a cropping system model and an economic model run sequentially. The study reveals that land productivity and farm income decline under climate change. Depending on the changes in precipitation, farm productivity falls by 15 to 20 percent and farm income 5 to 20 percent when the temperature increases moderately (1�C). As the climate warms up (2�C and 3�C), farm productivity and income are severely affected, by 35 to 55 percent and 45 to 70 percent, respectively. When simple adaptation strategies based on new management techniques for hard wheat are tested - more irrigation and fertilization - compensations for the negative effects of climate change are found to be worthwhile only for a 1�C increase in temperature. However, the success of adaptation strategies highly depends on the availability of more water and lower additional cost to mobilize them at the farm level.adaptation strategies, Bioeconomic modeling, Agriculture, Climate change, farm income, productivity,
Potential of tissue cultured medicinal plants in Malaysia
No full textMedicinal plants possess many secondary products that exhibit biological activities such as antioxidant, anticancer, anti-inflammatory, antibacterial and anti microbial. Scientific findings have demonstrated that tissue culture techniques could be an alternative tool to propagate plant in vitro and manipulate secondary metabolites in medicinal plants. This review aims to give an update on the various plant regeneration of some locally used medicinal plants in Malaysia such as Eurycome longifolia Jack, Zingiber officinale Roscoe, Centella asiatica L., Justicia gendarussa Burm. f, Kaempferia galanga L. and Orthosiphon stamineus Benth. Different type of cultures including organ, callus and cell cultures is also discussed
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