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Biomedical subjects

L Truong

Publications and source records attributed to L Truong.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pharmacokinetics of a 14C-labeled phosphorothioate oligonucleotide, ISIS 2105, after intradermal administration to rats.

After intradermal administration of 3.7 mg/kg of 14C-labeled 5'-TTGCTTCCATCTTCCTCGTC-3' (14C-labeled ISIS 2105) to rats, a phosphorothioate oligodeoxynucleotide, absorption was rapid. Approximately 65% of the administered dose was absorbed within 1 hr after the dose and peak blood levels were achieved within 30 min. After the initial rapid phase of absorption, a slower absorption phase ensued that resulted in more than 95% of the dose being cleared from the injection site. Slow metabolism of 14C-labeled ISIS 2105 occurred at the injection site. The rate and characteristics of metabolism in the skin were similar to those observed in other tissues. Once absorbed, the pharmacokinetics, distribution and metabolism of 14C-labeled ISIS 2105 after intradermal administration were comparable to those after an i.v. dose. The distribution and terminal half-lives were 0.5 and 53 hr, respectively. Levels of 14C-labeled ISIS 2105 in the blood were found in the plasma and the drug distributed broadly to all peripheral tissues; the liver, renal cortex and bone marrow accumulated the highest levels of drug. The 14C-labeled ISIS 2105 was eliminated principally by metabolism. Approximately 50% of the dose was found in expired air and 15% and 5% were found in urine and feces, respectively. No intact oligonucleotide was found in urine or feces at any time.

Absorption↗
PubMed1993

Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats.

5'-TTGCTTCCATCTTCCTCGTC-3' (ISIS 2105) is a phosphorothioate oligodeoxynucleotide currently being evaluated as an intralesional antiviral drug for the treatment of genital warts that are caused by the human papillomavirus. ISIS 2105, labeled with 14C (at the carbon-2 position of thymine) was administered as a single i.v. injection (3.6 mg/kg) to female Sprague-Dawley rats to assess the disposition of the drug. After i.v. administration of [14C]2105, blood radioactivity disappeared in a multiexponential manner with the half-lives of the phases equal to 0.4, 1.9, 7.1 and 5.1 hr. The initial volume of distribution was 22 ml and the postdistribution volume of distribution was 1076 ml, which indicated an extensive distribution of radioactivity. The apparent blood clearance was 14.7 ml/hr. The radioactivity in the expired air accounted for 51% of the administered dose over the 10-day period. Urinary and fecal radioactivity accounted for 15% and 5% of the administered dose, respectively. The major sites of radioactivity uptake were the liver (up to 22.6% of the dose), kidneys (renal cortex, up to 14% of the dose), bone marrow (up to 14% of the dose), skin (up to 13% of the dose) and skeletal muscle (up to 9% of the dose). Other tissues contained approximately 1% or less of the dose. The overall recovery of radioactivity 10 days postdosing was 95.1 +/- 7.5% (mean +/- S.D.) of the administered single dose. The radioactivity in the blood was almost completely in the plasma during the course of the study. In the plasma, the radioactivity was extensively bound to proteins, as assessed by size-exclusion high-performance liquid chromatography (HPLC), in samples up to 8 hr postdosing. Retention data on size-exclusion HPLC and in vitro incubations using purified proteins suggested that the plasma proteins that bound [14C]2105 were albumin and alpha 2-macroglobulin. The complex formed between the plasma proteins and [14C]2105-derived radioactivity was dissociated on anion-exchange HPLC to indicate that the great majority of plasma radioactivity coeluted with intact [14C]2105 in samples that contained sufficient radioactivity for analysis. There was a time-dependent decrease in the proportion of hepatic and renal radioactivity that coeluted with the intact [14C]2105 during the course of the study. The urine did not contain radioactivity that eluted with intact [14C]2105 on anion-exchange HPLC.

Animals↗
PubMed1992

Unusual glomerular lesion in a patient receiving long-term interferon alpha.

A 60-year-old man with long-standing chronic myelogenous leukemia presented with renal insufficiency and proteinuria after more than 6 years of therapy with daily interferon alpha injections. He also manifested unusual skin lesions and a low-titer antinuclear antibody (ANA). Percutaneous renal biopsy disclosed an unusual glomerular lesion characterized by global, diffuse, and marked widening of the lamina rara interna, and focal segmental mesangial proliferation. Discontinuation of the drug resulted in resolution of the proteinuria, but not the renal insufficiency. These glomerular changes have not been reported previously as a complication of this form of malignancy and are similar to lesions reported in newborn rats and mice receiving interferon alpha. The potential role of interferon alpha in the development of this glomerular disease is discussed.

Hand Dermatoses↗
PubMed1990

Characterization of the interstitial cellular infiltrate in experimental chronic cyclosporine nephropathy.

In a recently described rodent model of chronic cyclosporine nephropathy (CCN) (consisting of irregularly distributed areas of interstitial inflammation, interstitial fibrosis, and tubular atrophy) we have characterized the interstitial inflammatory cells. Using a modified avidin-biotin peroxidase technique, kidney tissue was examined with monoclonal antibodies directed against leukocyte-common antigen (LCA), T lymphocytes, T helper and T nonhelper lymphocytes, Ia (B cell marker), and macrophages. Injured cortex from cyclosporine-treated animals demonstrated increased numbers of T helper and B lymphocytes, macrophages, and cells bearing LCA. Cytotoxic (T nonhelper) cells were scant. Non-injured areas of cortex from CsA-treated animals demonstrated only a modest increase in macrophages when compared with vehicle controls and normal rats. We conclude that CCN in rodents is characterized by an interstitial inflammatory infiltrate of T helper cells, B cells, and macrophages. The role of these cells in the pathogenesis of CCN, however, remains speculative.

Animals↗
PubMed1990

Effects of chronic volume expansion and enalapril on chronic cyclosporine nephropathy.

Prolonged treatment with cyclosporine (CS) results in an irreversible renal lesion consisting of interstitial fibrosis and tubular atrophy, as well as prominent hyperplasia of the juxtaglomerular apparatus (JGA). Ischemia to the tubulointerstitial compartment caused by intense CS-mediated renal vasoconstriction may contribute significantly to the development of this lesion. To explore the potential role of volume contraction and activation of the renin-angiotensin system (RAS) in the genesis of this lesion, we have employed a recently described rodent model of chronic cyclosporine nephropathy (CCN). Over 28 days of CS therapy, animals received plain drinking water, 1% saline, or enalapril (ENAL), 50 mg/l in drinking water. At the end of 28 days, Na+ balance in saline-treated animals was markedly positive, and plasma volume was increased; however, glomerular filtration rate (GFR) did not change, and the tubulointerstitial lesion and JGA hyperplasia as evaluated by morphometric techniques were unaffected. Enalapril-treated animals were relatively hypotensive with lower GFR than CS controls. Enalapril conferred no protection against the development of tubulointerstitial disease and exacerbated the development of JGA hyperplasia and hyperkalemia. We conclude that volume contraction is not an important contributor to the reduced GFR, tubulointerstitial lesion, or JGA hyperplasia associated with long-term CS treatment. Blockade of the RAS also conferred no protection against the development of tubulointerstitial disease but resulted in worsening of JGA hyperplasia and hyperkalemia.

Animals↗
PubMed1989

De novo membranous glomerulonephropathy in renal allografts: a report of ten cases and review of the literature.

De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological features of ten patients with de novo MGN were studied and the related literature was reviewed to assess the clinical features, morphologic characteristics, and natural course of this disease. De novo MGN may occur in both living related and cadaveric allografts at any time after transplantation. It presents clinically either as asymptomatic proteinuria or the nephrotic syndrome, a feature of poor prognostic implication. Morphologically, de novo MGN in most instances has distinct differences from idiopathic MGN in native kidneys and is accompanied by varying features of rejection. About 50% of grafts which develop de novo MGN eventually fail. This rather poor outcome may not represent the natural history of de novo MGN per se but rather the consequences of associated chronic rejection. Evidence is presented that many of the cases of so-called de novo MGN may be a complication of transplant glomerulopathy rather than being caused by mechanisms totally independent from rejection.

Cadaver↗
PubMed1989

Effects of uninephrectomy and high protein feeding in cyclosporine nephropathy.

Using a recently described rodent model of chronic cyclosporine nephropathy (CCN), the effects of uninephrectomy (UNx) and high protein feeding on the development of CCN were studied. After 28 days of i.p. cyclosporine (Cs; 25 mg/kg/day) in UNx and sham nephrectomized (SNx) rats, the single kidney GFR was higher in UNx animals (0.55 +/- 0.09 vs. 0.29 +/- 0.05 ml/min, P less than 0.04) as was RPF (3.05 +/- 0.46 vs. 1.45 +/- 0.37 ml/min, P less than 0.04). Morphometric evaluation of the chronic tubulointerstitial lesion (TI) demonstrated lower scores and relative protection in the UNx group (16.48 +/- 3.52 vs. 64.76 +/- 18.30, P less than 0.01). In separate groups of rats undergoing UNx or SNx and subsequent treatment with Cs, dry kidney weights confirmed that compensatory renal hypertrophy was present in UNx animals. The modulating effect of dietary protein on the lesion of CCN was studied in UNx rats fed a 5% or 60% protein diet during the period of Cs treatment. At the end of the study period animals fed the high protein diet demonstrated a higher RPF (3.19 +/- 0.58 vs. 1.58 +/- 0.29 ml/min, P less than 0.04), higher GFR (0.55 +/- 0.07 vs. 0.35 +/- 0.04 ml/min, P less than 0.05) and lower TI score (64.45 +/- 17.35 vs. 130.32 +/- 23.48, P less than 0.04) when compared with animals consuming a low protein diet. We conclude that the relative renal vasodilation induced by partial ablation of renal mass and high protein feeding affords some protection against the development of CCN.

Animals↗
PubMed1989

Thyroid neoplasms containing mature fat: a report of two cases and review of the literature.

Thyrolipoma or adenolipoma of the thyroid, defined as a thyroid adenoma containing mature fat tissue, is rare and has been reported only seven times. Moreover, the presence of mature fat tissue has been described in only one case of thyroid carcinoma (papillary subtype). We describe one case of thyrolipoma and one case of fat containing follicular carcinoma of the thyroid, and we reviewed the literature on the presence of adipose tissue in the thyroid. It was found that aside from the above conditions, mature adipose tissue has been reported in diffuse lipomatosis of the thyroid, some amyloid goiters, a colloid goiter, and even some normal thyroids. Aside from the presence of mature fat tissue, the clinicopathologic features of fat containing thyroid tumors are not different from those of their usual counterparts.

Adenocarcinoma↗
PubMed1988

Chronic cyclosporine nephrotoxicity. A rodent model.

The lack of a suitable rodent model has hampered the study of chronic cyclosporine nephrotoxicity. Proximal tubule vacuolization and inclusions are consistently reported in rat studies, but changes associated with chronic CsA nephrotoxicity in humans (interstitial fibrosis, tubular atrophy, arteriolopathy) are difficult to reproduce. Using male Sprague-Dawley (SD) rats we have administered CsA in olive oil (o.o.) at 25 mg/kg/d i.p. for 28 consecutive days. This protocol consistently results in a lesion of patchy interstitial fibrosis, tubular atrophy, interstitial inflammation, and marked juxtaglomerular apparatus (JGA) hypertrophy and hyperplasia. Control animals were pair-fed and received only o.o. i.p. Despite pair feeding, CsA-treated animals gained only 9.4 +/- 12 g, while controls gained 69 +/- 18 g. Minimal JGA hypertrophy was noted in some control animals, but no other significant changes were identified. The protocol was well tolerated and did not result in peritonitis. GFR was significantly depressed in the CsA-treated animals at the end of the 28-day period (0.44 +/- .26 vs. 1.12 +/- .13 ml/min) and BP tended to be lower, but this difference did not achieve statistical significance. We conclude that this model results in a reproducible lesion with many of the features of chronic CsA nephrotoxicity in humans, and that it will permit study of this problem to advance.

Animals↗
PubMed1988

Presence of the Dr receptor in normal human tissues and its possible role in the pathogenesis of ascending urinary tract infection.

The Dr hemagglutinin of uropathogenic Escherichia coli recognizes the Dra blood group antigen, a component of the IFC or Cromer-related blood group complex. The present report used the Dr hemagglutinin to demonstrate location of the Dr receptor in selected human tissues and to evaluate the possible use of this lectin as a tissue marker recognizing sites sensitive for bacterial colonization. It was found that the Dr receptor was expressed in different parts of the digestive, urinary, genital, and respiratory tracts, and skin. Intense staining by Dr hemagglutinin was shown in colonic, bronchial, and endometrial glands, and skin eccrine sweat glands. Structures of the urinary tract showing strong fluorescence were renal tubular basement membrane, Bowmans' capsule, and transitional epithelium. The role of Dra antigen as receptor for adhesion for Dr-positive E. coli in ascending colonization of urinary tract and the possible importance of Dra in human pathology is discussed.

Antigens, Bacterial↗
PubMed1988

Immunohistochemical demonstration of the endothelial nature of aortic intimal sarcoma.

Primary sarcomas of the aorta are rare; fewer than 30 cases have been reported. Among these, the majority are intraluminal and apparently intimal in origin. Extensive histochemical and electron-microscopic evaluation of these tumors has not previously been performed. We present a case of aortic intimal sarcoma in a 70-year-old man whose resected aorta showed multifocal, intimal tumor that appeared on light microscopy to be undifferentiated sarcoma. Electron microscopy was not helpful; however, immunohistochemical studies confirmed the endothelial nature of this neoplasm. The multifocal pattern of the tumor and the presence of intervening, atypical, proliferative endothelial cells suggests that endothelial dysplasia may have been a precursor lesion.

Aged↗
PubMed1986

Florid reactive periostitis.

A case of florid reactive periostitis of the thumb is reported. This rare, benign, bone-producing lesion is easily confused with osteosarcoma. It is also known as parosteal or nodular fascitis. Careful histologic and radiographic evaluations are needed to establish the diagnosis and avoid unnecessary amputation. Marginal excision seems to be adequate treatment.

Adult↗
PubMed1985

Intravenous pyogenic granuloma of the ocular adnexa. Report of two cases and review of the literature.

Intravenous pyogenic granuloma is a recently described form of pyogenic granuloma (PG) in which the angiomatous proliferation is confined entirely within the lumen of a vein. To our knowledge, only four cases involving the ocular adnexa, including two that we encountered, have been described. Histologically, this benign lesion is similar to PG of other locations and is characterized by lobular congeries of capillaries embedded in a fibromyxoid matrix containing scattered chronic inflammatory cells. The whole lesion appears as a single polypoid mass projecting into the lumen of a dilated vein. The histogenesis of this lesion remains obscure. Complete local excision is the treatment of choice. Intravenous PG can be differentiated from other intravascular fibroangiomatous proliferations, including intravascular papillary endothelial hyperplasia, intravenous atypical vascular proliferation, intravascular fasciitis, and organized thrombus.

Adult↗
PubMed1985

Temporal arteritis and renal disease. Case report and review of the literature.

Renal abnormalities have been described in a small percentage of patients with temporal arteritis. Transient microscopic hematuria is the most common finding. In rare instances, widespread vasculitis involving renal arteries or microscopic polyarteritis nodosa can be seen. This case report describes the association of temporal arteritis with membranous glomerulonephropathy and the nephrotic syndrome in an elderly patient, an occurrence not previously reported. Whether this association is coincidental or pathogenetically linked remains to be determined.

Aged↗
PubMed1985

Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion.

Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion.

Adrenal Cortex Hormones↗
PubMed1981

Presence of conjugated catecholamines in rat brain: a new method of analysis of catecholamine sulfates.

A new method of measuring catecholamine (CA) sulfate permitted us to detect its presence in rat brain for the first time. The procedure consisted of separating the CA sulfate from the free CA by alumina adsorption followed by passage through Dowex, and measuring the CA sulfate by a radioenzymatic assay in the presence of a sulfatase. This method permitted demonstration of the presence of dopamine sulfate, and occasionally, of norepinephrine and epinephrine sulfate in the hypothalamus, striatum, and hippocampus of rat brain.

Animals↗