Severe mucosal involvement in a patient with cutaneous leishmaniasis from Nepal.
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Biomedical subjects
Publications and source records attributed to M Jacob.
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The purpose of the present study was to apply melt granulation in a fluidized bed dryer (fluidized bed dryer melt granulation) to manufacture one-step effervescent granules composed of anhydrous citric acid and sodium bicarbonate to make tablets. This study permitted us to establish that such process parameters as concentrations of polyethylene glycol (PEG) 6000, residence times in the fluidized bed dryer, fineness of PEG6000, fineness of initial mixture effervescent systems, and efficiency of two lubricants markedly affect some granule and tablet characteristics. It is a dry process that is simple, rapid, effective, economical, reproducible, and particularly adapted to produce effervescent granules that are easily compressed into effervescent tablets.
In the present study we apply melt granulation in an air forced oven, called "are forced oven melt granulation" to the single-stage manufacture of effervescent granules consisting of anhydrous citric acid (43.2%) and sodium bicarbonate (56.8%) in order to make tablets. This study established that process parameters such as concentration of PEG 6000, residence time in the air forced oven, fineness of PEG 6000, fineness of the initial effervescent mix and efficiency of two lubricants markedly influenced several granule and tablet characteristics. The granules ready to be compressed into tablets were stable for 7 days at 60% RH/18 degrees C. It is a dry, simple, rapid, effective, economical, reproducible process particularly well suited to the manufacture of effervescent granules which are easily compressed into effervescent tablets. Of all the formulations tested, only formulations B2 and E2 melt granulated for 30 minutes gave tablets which had optimum compression characteristics without processing problems during compression.
A protein chain must move relative to the solvent molecules and explore many conformations when it folds from the extended unfolded state to the compact native state. Experimental and theoretical approaches suggest that diffusional processes in fact contribute to the kinetics of protein folding. We describe here how variations of the solvent viscosity can be employed to uncover the diffusional contributions to a folding reaction and assess the use of transition state theory and Kramers' rate theory for the analysis of protein folding reactions.
A pressure-jump apparatus was employed in investigating the kinetics of protein unfolding and refolding. In the reaction cell, the pressure can be increased or decreased by 100-160 bar within 50-100 microseconds and then held constant. Thus, unfolding and refolding reactions in the time range from 70 microseconds to 70 s can be followed with this technique. Measurements are possible in the transition regions of thermally or denaturant-induced folding in a wide range of temperatures and solvent conditions. We used this pressure-jump method to determine the temperature dependence of the rate constants of unfolding and refolding of the cold shock protein of Bacillus subtilis and of three variants thereof with Phe --> Ala substitutions in the central beta-sheet region. For all variants, the change in heat capacity occurred in refolding between the unfolded and activated states, suggesting that the overall native-like character of the activated state of folding was not changed by the deletion of individual Phe side chains. The Phe27Ala mutation affected the rate of unfolding only; the Phe15Ala and Phe17Ala mutations changed the kinetics of both unfolding and refolding. Although the activated state of folding of the cold shock protein is overall native-like, individual side chains are still in a non-native environment.
OBJECTIVE: To compare methods for assessing changes in body composition during gonadal hormone replacement therapy in a group of HIV-positive men with AIDS wasting syndrome. DESIGN: The study included a 21-day, double-blind, randomized, placebo-controlled inpatient intervention and a 12-week open-label intervention. The inpatient intervention included 18 men who were confined to a metabolic ward. Days 1-7 comprised weight stabilization and body composition measures followed by 14 days of nandrolone decanoate at either 65 or 195 mg weekly, or placebo, and repeat testing. The open-label intervention comprised 12 weeks of 200 mg nandrolone decanoate fortnightly with measurements of fat-free mass at 6 and 12 weeks. METHODS: The inpatient intervention measured nitrogen balance from 24 h urine and fecal collections and fat-free mass by dual energy x-ray absorptiometry (DEXA), bioimpedance spectroscopy (BIS) and D2O dilution. Nitrogen balance was calculated as the difference between dietary intake and urinary and fecal nitrogen excretion. Nitrogen was converted to fat-free mass using the constant of 32.5 g. Repeated measures analysis of variance was used to determine which methods were significantly different from the reference nitrogen balance technique. RESULTS: Nitrogen accretion of lean tissue was 0.55 and 0.85 kg weekly for low and high-dose groups, respectively. Estimated nitrogen retention during the open-label study was 0.42 kg weekly. Body weight increased with the estimated lean tissue accretion. DEXA, BIS and D2O methods demonstrated improvements in fat-free mass, although the BIS estimate of fat-free mass most closely matched the results of the nitrogen retention method. CONCLUSION: DEXA, BIS and D2O techniques demonstrated increases in fat-free mass. The BIS method is less costly, more convenient to use, and had results that more closely matched those from nitrogen balance and retention methods. BIS may be the preferred method to monitor changes in fat-free mass in AIDS patients and patients with malnutrition.
The rostral part of the notochord reveals many peculiarities compared with the trunk mesoderm. Furthermore, its role in head formation and inductive processes in the head is not as well understood as the interaction of the trunk notochord with the spinal cord and somites. To interpret experimental and molecular biological examinations in the developing head region, exact knowledge about morphological features of the rostral notochord is fundamental. Here we show that the rostral notochord reveals variations that depend on species and individual. We describe morphological characteristics of the rostral (head) notochord in human embryos (Carnegie stages X-XIV), which are shown in semithin sections and three-dimensional graphic reconstructions. Special attention is paid to the relationship of the notochord with the prechordal mesoderm and the adenohypophysis. We propose that in the human the rostral notochordal tip terminates at Rathke's pouch, whereas in the chick prechordal mesoderm is found in between the notochordal tip and the anlage of the adenohypophysis. The behaviour of the notochord at the end of the embryonic period proper and early fetal time is shown in sagittal histological sections of 16 to 49 mm CRL human embryos. Position and disintegration of the rostral notochord is also described in embryos of cat (8-25 mm), mouse (stage 21-24 according to Theiler) and chicken (stage 22-26 HH). A synopsis reveals the different course of the notochord within, at the inner or outer side of the basioccipital cartilage. The course of rostral notochord is determined by its attachment points at the hypophysis, the pharynx or the footplate of the brain. In all species, it has an undulating course. Its rostral tip is highly coiled, and fragments or splinters are found within the anlage of the dorsum sellae. Thus, we have reasons to believe that the adenohypophysis is a hindrance for the rostral elongation of the notochord. Variable adhesions between notochord and pharyngeal epithelium are considered to be responsible for invaginations of the pharyngeal wall forming bursae pharyngeae. In contrast to other authors, we observed in the mouse that rostrally the notochord bends ventral and penetrates the chondrocranium at the level of the later synchondrosis basisphenoidale to build a bursa pharyngea. Finally, partial duplications of two human notochords are described.
OBJECTIVE: Our purpose was to show that biomechanical alterations toward and away from normal on x-ray studies may be the result of changes in temporomandibular joint dysfunction and to discuss possible neurologic explanations for this phenomenon. CLINICAL FEATURES: Two patients are discussed; the first had migraine headache symptoms, and the second had chronic hypomobility of mandibular opening, dizziness, headache, and neck pain and stiffness. In both patients mensuration changes in different types of cervical x-ray studies were noted in conjunction with exacerbation of, and elimination of, temporomandibular joint dysfunction. INTERVENTION: Comanagement of these cases was done with dental professionals. Chiropractic treatment included vectored/linear, upper cervical, high-velocity, low-amplitude chiropractic manipulation of the atlas vertebra, diversified manipulation, myofascial therapy, stretch and spray procedures, and soft tissue manual techniques. CONCLUSION: Temporomandibular joint dysfunction may cause cervical muscular and spinal biomechanical changes that may become visible and change on x-ray examination. Further investigation into this phenomenon is recommended.
There has been some debate as to whether protein folding involves diffusive chain motions and thus depends on solvent viscosity. The interpretation of folding kinetics in viscous solvents has remained difficult and controversial, in that viscogenic agents affect folding rates not only by increasing solvent viscosity but also by increasing protein stability. By carefully choosing experimental conditions, we can now eliminate the effect on stability and show that the folding dynamics of the cold shock protein CspB are viscosity dependent. Thus Kramers' theory of reaction rates rather than transition state theory should be used to describe this folding reaction.
The erythrokeratodermas are a distinct but clinically variable group of rare geno-dermatoses, characterized by circumscribed erythematous and hyperkeratotic lesions. All attempts to establish a valid classification have been based on purely clinical and morphologic criteria. Erythrokeratoderma en cocardes, also known as genodermatose en cocardes or Degos' syndrome, was first described by Degos in 1947. The condition is characterized by large round plaques with concentric erythema and scaling having a target configuration, which remit and recur, in addition to scaly plaques as seen in erythrokeratoderma variabilis. A case of this rare genodermatosis is described.
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Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drying technique. The influence of factors such as polymer concentration, inlet temperature, and drug/polymer ratio were investigated. The product yields were a function of the type and concentration of the polymer, with the highest values being reached from feeds containing 1% MCC and EC. Parameters of 1% polymer concentration and an inlet temperature of 140 degrees C gave rise to optimal processing conditions. Using these parameters, the influence of some adjuncts, such as polyethylene glycol 6000 (PEG 6000), dibutyl sebacate (DBS), polyvinylpyrrolidone (PVP), and carboxylic acids such as citric acid (CA), phthalic acid (PA), succinic acid (SA), tartaric acid (TA), and oxalic acid (OA), on the spray-drying process was evaluated. Of the additives tested, PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield decreases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for carboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 47%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolution studies in pH 1 dilute HCl and pH 6.8 phosphate buffer dissolution media showed that formulations consisting of 1% polymer with a drug/polymer ratio of 1/1 exhibited the slowest drug release, with the spheroids coated with NaCMC and HEC showing the longest T50% values (with 45 and 53 min at pH 1 and 49 and 55 min at pH 6.8, respectively). Slightly better sustained drug release in pH 6.8 dissolution medium was reached, showing the following trend: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in acidic pH 1 dissolution medium and PVP > OA > TA > SA > PA > CA > DBS in phosphate buffer at pH 6.8.
In vertebrates, the female reproductive system arises from the Müllerian (paramesonephric) duct which develops in both sexes under the influence of the Wolffian (mesonephric) duct. For a better understanding of the interactions between the Müllerian duct and its adjacent tissues, we present a systematic scanning and transmission electron microscopic investigation of early stages of avian Müllerian duct development. This starts within the cranial part of the Müllerian ridge from a placode-like thickening and deepening of the coelomic epithelium containing nephrostomes as remnants of the last pronephric and first mesonephric tubules. Groups of cells detach from this placode and rapidly expand caudally as a solid cord. This becomes canalized, but the tip region remains mesenchymal and is found enclosed within the basal lamina of the Wolffian duct. Immunostaining reveals that the Müllerian duct migrates within a matrix rich in laminin and entactin. When the canalized duct has opened into the coelomic cavity, one or more secondary ducts are found immediately caudal of the main funnel, for a short period only, possibly to supply material to the expanding duct. BrdU-anti-BrdU reaction reveals a high proliferation of the duct epithelium. The thickened epithelium of the Müllerian ridge dissolves to form the mesenchymal layers of the duct. Immunostaining with vimentin argues against a cellular contribution of Wolffian duct cells to the Müllerian duct. Comparing the data from avian embryos with those of human indicates that the modalities of early Müllerian duct development are similar in both species.
Since Mycobacterium leprae are rarely demonstrable in the tuberculoid spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on the basis of finding active destruction of cutaneous nerves by granulomatous inflammation in a skin biopsy. Immunoperoxidase staining for S-100 protein, which is a marker for Schwann cells, was used to delineate nerves in lesional skin biopsies of 25 patients with tuberculoid and borderline tuberculoid leprosy as well as 15 controls with nonleprous granulomatous inflammation. Four different patterns of nerve damage were observed: infiltrated, fragmented, absent, and intact. All of the nonleprous granulomatous dermatoses showed only intact nerves, either inside or outside the granuloma, and so S-100 staining can be used to rule out leprosy.
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The polymorphism of the equimolar mixture of 1-palmitoyl-2-arachidonoyl-phosphatidylethanolamine (PAPE) and dimyristoyl-phosphatidylmethanol (DMPM) was examined by infrared and 31P nuclear magnetic resonance spectroscopy to determine the suitability of this widely used but yet uncharacterized lipid mixture as a phospholipase A2 substrate. The results show that the mixture undergoes a gel-to-liquid crystalline phase transition between 12 and 35 degrees C. The transitions of the individual lipids were also examined. We report that the temperature of the gel-to-liquid crystalline phase transition of DMPM is 40 degrees C. At 2 degrees C, PAPE exists in the fluid lamellar form. This lipid undergoes a lamellar-to-inverted hexagonal phase transition at 31 degrees C. In conclusion, the equimolar PAPE/DMPM mixture forms fluid lamellar phase at the physiological temperature. However, the upper end of the gel-to-liquid crystalline phase transition of the mixture is really close to the physiological temperature and this situation is a serious source of potential artefacts.