Biomedical subjects
Publications and source records attributed to A Nangia.
The crystal structures of trimethyl isocyanurate, C6H9N3O3, (1), and triethyl isocyanurate, C9H15N3O3, (2), contain topologically similar C--H...O hydrogen-bonded networks. In (1), there are two symmetry-independent molecules and each forms its own layer structure. In (2), two of the ethyl groups point one way with respect to the heterocyclic ring, while the third points in the opposite direction.
Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare, incompletely characterized variant that must be distinguished from similar tumors of bladder or gastric origin. In this study, we used mucin and immunoperoxidase stains on formalin-fixed, paraffin-embedded sections from 12 prostatic adenocarcinomas with SRC components, with antibodies to prostate-specific antigen (PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a comparison study on six bladder and seven gastric carcinomas with SRCs. The prostatic SRC component was always associated with the usual high-grade adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12 cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7 (9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1 proliferation index was 8%. Intracellular mucin was identified (periodic acid-Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of 10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3 cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2 (5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%, respectively. All were negative for cytokeratin 34 beta E12. We conclude that prostatic adenocarcinomas with SRC components are typically accompanied by high-grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and CD44 similar to that shown by high-grade adenocarcinoma components; have a low MIB-1 proliferation index; and are not always distinguishable from SRC components of bladder and stomach carcinomas with any of the above stains, including PSA.
Previously, we have investigated the relationship between dissociation constant (pKa) and skin irritation potential. In the present experiment, 12 basic compounds, with varying pKa values ranging from 1.4 to 11.2, were applied on the backs of 12 healthy adult panellists. Cutaneous reactions were measured objectively, using reflectance spectroscopy and transepidermal water loss (TEWL), and evaluated subjectively with a modified Draize scale. A positive correlation between increasing pKa and skin irritation capacity, measured either visually or by reflectance spectroscopy, was found, but only mecamylamine (pKa = 11.2) induced a significant increase in transepidermal water loss. Compounds with low pKa also induced a paradoxical vasoconstriction measured by reflectance spectroscopy. Only high pKa appeared predictive of in vivo skin irritation, and these chemicals apparently induce skin irritation with only minimal disruption of the skin barrier. A simple 1-variable model is predictive of skin irritation for this series of organic permeants with increasing pKa.
The effects of the application of skin irritants on the in vitro percutaneous absorption of three model compounds of diverse physico-chemical properties, caffeine, indomethacin, and hydrocortisone, were investigated. Norephedrine and imipramine, basic drugs with a known skin irritation potential, were employed to damage the skin. Treatment with norephedrine increased the permeation of caffeine and hydrocortisone by two- to fourfold, while absorption of indomethacin declined an order of magnitude. A similar result was obtained for the effect of treatment with imipramine on transport of caffeine. Pretreatment with imipramine promoted hydrocortisone absorption 10-fold but, unlike norephedrine, did not alter indomethacin permeation. While both treatments in vivo caused an increase (norephedrine > imipramine) in the pH on the surface of skin and after tape-stripping the skin, only norephedrine caused changes in transepidermal water loss in vivo in man. Since imipramine was the more severe irritant as judged by erythema, alterations by irritants of barrier function appeared rather complex.
BACKGROUND: The efficacy of octreotide in the regulation of endocrine tumor secretion and symptomatology has been well documented. Its effects on neuroendocrine tumor generation and cell proliferation are less well understood. The purpose of this study was to determine if blockade of somatostatin receptors by octreotide would alter gastrin levels and influence enterochromaffin-like (ECL) cell proliferation. METHODS: The well-established gastric ECLoma model of the rodent, mastomys, was used. Animals received loxtidine (1 mg/kg/day), an irreversible H2 blocker, and subcutaneous slow release, octreotide pellet implants (150 or 300 micrograms/kg/day) or placebo pellets for a 4-month period. RESULTS: Control parameters for gastric mucosal thickness, plasma gastrin level, ECL cell density, and bromodeoxyuridine-positive cells were 517 +/- 20 microns, 46.1 +/- 11.4 pmol/L, 7.4 +/- 0.9 cells/visual field, and 13.8 +/- 2.6 cells/visual field, respectively. After loxtidine-placebo treatment all values were significantly increased (p < 0.05; 883 +/- 70 microns, 192.8 +/- 10.6 pmol/L, 97 +/- 16.2 cells/visual field, and 51.7 +/- 19.2 cells/visual field, respectively). High dose octreotide significantly inhibited all parameters (668 +/- 3.5 microns, 66.2 +/- 20.5 pmol/L, 37.0 +/- 8.0 cells/visual field, and 10.9 +/- 2.2 cells/visual field; p < 0.05). Low dose octreotide failed to significantly inhibit ECL cell density mucosal thickness, or cell proliferation. CONCLUSIONS: Irreversible H2 receptor blockade results in hypergastrinemia and ECL cell tumor generation. Hypergastrinemia, ECL cell hyperplasia, and cell proliferation are significantly inhibited by in vivo blockade of somatostatin receptors by administration of octreotide.
Advances in our knowledge of the wound healing process has led to the development of various synthetic skin substitutes, which when applied to the wound surface provide a microclimate conducive to healing. The requirements of an ideal temporary skin substitute are presented. This review also provides an updated account of the preclinical evaluation procedures utilized to assess these demands, particularly important parameters such as water vapour permeability, adherence to excised wound surface, oxygen permeability, mechanical properties, microbial permeability and exudate soaking capacity.
Attention is increasingly being focused on the relationship of dissociation constant (pKa) of chemicals and skin irritation presumably caused by pH effects at epidermal levels. Human skin studies of irritation have utilized both subjective visual-palpation scores and reflectance spectroscopy (RS) or laser Doppler velocimetry (LDV) respectively. Several studies document that erythema determined subjectively and objectively correlates with the degree of skin irritancy, but others report lack of correlation between LDV and irritancy scored subjectively. In this study, pharmacological and chemical in vivo skin irritation was evaluated utilizing an improved reflectance spectrophotometer equipped with computerized data analysis. In 16 white females, a model for skin irritation was induced by a 24-h patch application of 4 basic chemicals, imipramine, norephedrine, nicotine and 8-aminoquinoline, with pKa'S ranging from 3.8 to 9.5. Skin pigmentation (melanin) and the relative amounts of oxygenized (arterial) and deoxygenized (venous) hemoglobin present in the erythematous skin were calculated. A clear increase in the hemoglobin content was observed in chemical and vehicle exposed sites. Although skin irritation is a complex phenomenon involving chemical and solution properties, percutaneous absorption and the biological drug response, high pKa (p greater than 0.01) was predictive of acute skin irritation in man using computerized analysis of reflectance spectroscopy. A high correlation between visual score and RS was found (r = 0.91).
A simple and sensitive method is described for the determination of fluoroquinolones by HPLC on a C-18 column using fluorescence detection. Using a mobile phase of 25% (v/v) acetonitrile phosphate buffer (pH 2.0), adequate retention and separation among the solutes norfloxacin, amifloxacin, enoxacin, and pipemidic acid have been obtained using sodium lauryl sulphate as the pairing ion and tetrabutylammonium bromide as the counter ion. The chromatographic conditions selected have been used for the quantitation of norfloxacin, amifloxacin, and enoxacin in human plasma using pipemidic acid as the internal standard. A simple single-step protein precipitation procedure has been employed for pretreatment of plasma samples. The detection limits of the assay for enoxacin, amifloxacin, and norfloxacin are approximately 100, approximately 10, and approximately 20 ng/mL, respectively. The method has been employed for the determination of amifloxacin in plasma samples from a healthy volunteer following oral administration of a 400-mg amifloxacin capsule.
The important requirements of a skin substitute such as water vapour permeability, adherence to the excised wound surface, oxygen permeability, mechanical properties, impermeability to micro-organisms and exudate soaking capacity have been highlighted. Two commercial synthetic skin substitutes, Bioclusive and Geliperm, have been used to establish the preclinical assessment procedures for skin substitutes. Two in vitro techniques, the 'Water Cup' and the 'Inverted Cup,' and two in vivo methods involving a 'Ventilated Hygrometer Chamber' system and an Evaporimeter have been employed to assess and compare the water vapour permeability of the skin substitutes under controlled conditions. An Evaporimeter, which is very simple to operate, provides more accurate results. A simple test has been designed to evaluate the early adherence of the skin substitutes to the excised wound surface of rats. The pulling force and the peeling force required to remove the membrane from the wound surface have been measured and these forces have been found to depend upon the composition of the membrane. An oxygen permeability cell has been fabricated which measures the dissolved oxygen permeability of the skin substitutes. The detection of oxygen is based on the electrocatalytic reduction of oxygen at the surface of a noble metal. The tensile properties of the skin substitutes have been measured by an International Standard procedure and both the skin prostheses are associated with some drawbacks. An in vitro method of testing the microbial permeability of the skin substitutes has been designed which simulates an oozing colonized wound that a skin substitute faces in cases of septicaemia. Both the test materials were impermeable to both bacteria and fungi and will provide an effective barrier. The effectiveness of the skin substitutes to absorb wound exudate from the wound surface has been evaluated by soaking the pieces of the membranes in water, plasma and serum and observing their weight gain. The soaking capacity depends upon the composition and nature of the material. The procedures developed have been employed to evaluate a hydrogel type synthetic skin substitute recently formulated in our laboratory.
A new hydrogel-type skin substitute (HSS) has been investigated for its effectiveness in the management of excised wounds in rats and compared with Geliperm and Bioclusive and air-exposed control. Wound repair has been assessed by measuring the wound size and by histological examination. The effectiveness of the skin substitutes on the re-establishment of the cutaneous barrier to evaporative water loss (EWL) has also been examined by an Evaporimeter. When compared with Geliperm and Bioclusive, a faster rate of wound healing with complete epithelialization was observed under HSS. A significant improvement in the rate of restoration of the barrier functions was observed between the HSS-covered wounds and uncovered controls. A biphasic behaviour of EWL, with an initial rise followed by an exponential decline, was observed in uncovered control and wounds covered with Geliperm and HSS. In the case of Bioclusive, the decline in EWL was less pronounced.
Hydrocolloid dressings composed of dextran, phospholipid, glycerol and sodium lauryl sulphate have been formulated. A ventilated hygrometer system has been used to study the evaporative water loss (EWL) from the excised wound of rats with and without these dressings. A statistical experimental design has been used to locate a formulation which is flexible and semiocclusive in nature. The phospholipid component of the dressing has a significant role in controlling water vapour permeability of the dressing. The EWL from the excised wound covered with the optimized dressing has been compared with that for two commercial products.
Cocaine was administered as 1-, 2-, and 4-mg/kg intravenous bolus doses to each of six sheep. Plasma samples were collected as a function of time and assayed for cocaine using reversed-phase ion-pair HPLC. The assay involved double extraction with ether and UV detection at 229 nm. Using 2 mL of plasma, levels of 1 ng/mL of cocaine can be measured. The concentration versus time data obtained for the plasma samples were analyzed by a "noncompartmental" method. The pharmacokinetic parameters of cocaine in sheep had mean values of 4.0 L/kg, 3.5 L/kg, and 0.29 L X min-1 X kg-1 for Vd, Vdss, and CL respectively. The clearance of cocaine in sheep was much higher than cardiac output. Pulmonary first-pass effect has been suggested as the possible explanation for the large clearance of cocaine in sheep.
Staphylococcal protein A could be extracted in large amounts by simple stirring of the cells with physiological saline (pH 7.8). The amount of protein A obtained by the technique was found to be the same as obtained by lysozyme/lysostaphin techniques (45 micrograms/ml). The protein A extracted by salt-washing technique was of higher molecular weight (71,000) and differing in some biological properties like complement fixation from the protein A prepared by lysostaphin technique.
BACKGROUND: Malakoplakia is an uncommon but distinctive granulomatous disease, characterized by an accumulation of histiocytes or Von Hansemann cells containing intracytoplasmic, laminated Michaelis-Gutmann bodies. CASE: A 3-year-old male presented with a tender swelling in the left gluteal region that had been present for one month. Smears made from a fine needle aspirate showed large histiocytic cells containing intracytoplasmic, basophilic, laminated, targetoid Michaelis-Gutmann bodies resembling Von Hansemann cells in malakoplakia. Histopathology confirmed the diagnosis of malakoplakia of bone. CONCLUSION: This case, histologically proven to be malakoplakia, demonstrated regression of the lesion following therapy. The characteristic cytologic features and presence of Von Hansemann cells may in themselves be diagnostic and obviate the need for biopsy.
BACKGROUND: Localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) is a benign, slowly growing lesion with a peak incidence in the third to fifth decade of life. It is thought to arise from the synovium of tendon sheaths, frequently affecting interphalangeal joints of the hands, feet, ankles and knees. Although the histopathologic appearances are well established, only a few reports describe the cytomorphology of this lesion. CASE: A 37-year-old female presented with a slowly growing, nontender mass located near the left ankle joint. The cytologic features of localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) include abundant mononuclear histiocytic cells occurring singly and in three-dimensional tissue fragments, hemosiderin within histiocytes and a few multinucleated giant cells. Subsequently, the histopathologic examination of the surgical specimen was proven to be TGCT-L. CONCLUSION: Fine needle aspiration cytology can be used as a diagnostic tool for early and accurate detection of TGCT-L since the cytologic features combined with clinical details are sufficiently distinctive.