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Biomedical subjects

M F Khan

Publications and source records attributed to M F Khan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.

BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.

Adult↗
PubMed1998

Phenylhydroxylamine: role in aniline-associated splenic oxidative stress and induction of subendocardial necrosis.

To elucidate the role of N-phenylhydroxylamine (PHA, N-hydroxylated metabolite of aniline) in the selective toxicity of aniline to the spleen, dose-dependent studies were conducted with PHA in rats. Male Sprague-Dawley rats were given four doses each (1 dose/day) of 0.025, 0.05, 0.1, or 0.2 mmol/kg PHA in 0.5 ml of aqueous agar (0.25%) by gavage. The control animals received an equal volume of vehicle only. The animals were euthanized 24 h following the last dose. PHA toxicity in the blood was evident from a dose-dependent increase of methemoglobin. The most affected organ was spleen, which appeared dark and enlarged (splenomegaly) and showed increased spleen-to-body weight ratios, which were 28, 40, 66, and 87% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. Splenic lipid peroxidation (malondialdehyde content) was higher in all PHA-treated groups, whereas splenic protein oxidation (carbonyl content) increased in only the 0.05, 0.1, and 0.2 mmol/kg groups. The total iron content in the spleen also showed increases of 88, 135, 168, and 209% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. These biochemical changes were accompanied by a dose-dependent vascular congestion in the spleen, a characteristic feature of aniline toxicity. Although the ratio of organ to body weight increased for both testes and heart at the highest dose, striking morphological changes were observed only in heart. The cardiac lesions consisted of a both acute and resolving multifocal subendocardial necrosis involving predominently the left ventricle. Our results suggest that PHA is a splenotoxin and thus contributes to the toxicity of aniline, while at a high dose, it is also cardiotoxic, perhaps due to anoxia associated with the marked methemoglobinemia. These results further support the involvement of oxidative stress in the splenotoxicity of aniline which may be caused by its reactive metabolite(s) such as PHA.

Aniline Compounds↗
PubMed1998

Study of microleakage at Class I cavities prepared by Er:YAG laser using three types of restorative materials.

OBJECTIVE: The purpose of this in vitro study were to investigate microleakage at class I cavities filled with amalgam, composite resin, or glass-ionomer after preparation by Er:YAG laser and to compare the results with those by a conventional method using an air turbine. SUMMARY BACKGROUND DATA: There has been no report of a study of microleakage on class I cavities prepared by Er:YAG laser. METHODS: Ninety-six extracted human premolar and molar teeth were used in this study. Forty-eight class I cavities were prepared by Er:YAG laser and 48 class I cavities by air turbine. After preparation, each of the 2 groups was further subdivided into 3 groups, respectively, and cavities in each of these subgroups were filled by 1 of 3 types of restorative materials. Microleakage at the restored cavities was assessed by the dye penetration method and scanning electron microscopy (SEM). RESULTS: Minimal or moderate leakage was evident at most of the composite resin or glass-ionomer restorations, whereas moderate or severe leakage was observed at most of the amalgam restorations as shown by the dye penetration method. There was significant difference among the 3 restorative materials (p < 0.05), but there was no significant difference in microleakage between the cavities prepared by Er:YAG laser and those by air turbine (p > 0.05). SEM evaluation demonstrated good adaptation with most of the composite resin or glass-ionomer restorations, but amalgam restorations showed slightly poorer adaptation. CONCLUSION: These results suggest that Er:YAG laser is useful for class I cavity preparation from the viewpoint of microleakage.

Composite Resins↗
PubMed1998

The role of liver transplantation in the subacute trauma patients.

Two case reports are presented involving complex liver traumas requiring the need for liver transplantation. Both of these patients were designated unsalvageable until the transplant team was consulted. It is imperative that surgeons involved with complex hepatic trauma not give up hope and include these patients as potential liver recipients when irreversible liver failure occurs.

Adult↗
PubMed1997

Differential induction of polyamine oxidase activity in liver and heart of iron-overloaded rats.

The present study was undertaken to investigate the effect of iron dextran treatment on polyamine oxidase (PAO) activity, iron accumulation, and lipid peroxidation in livers and hearts of rats. PAO catalyzes oxidative deamination of polyamines, the cellular aliphatic cations. This reaction produces highly toxic hydrogen peroxide, 3-acetamidopropanal, and precursors of higher polyamines. The rats were given iron dextran daily for 7 d. In iron-dextran-treated rats, a marked increase in the hepatic level of iron was associated with enhanced lipid peroxidation and increased PAO activity. Though iron accumulation and lipid peroxidation in the iron-treated rats increased significantly in the heart, PAO activity remained unchanged. The paraffin sections of livers stained with Perls iron stain showed the presence of iron in macrophages and hepatocytes. The sections of hearts showed iron deposits only in macrophages, while myocytes showed no iron staining. These results show that although iron dextran treatment results in accumulation of iron in both liver and heart, it induces PAO activity only in liver. The significance of increased PAO activity in lipid peroxidation and fibrosis in iron-mediated injury is discussed.

Animals↗
PubMed1997

Acute hematopoietic toxicity of aniline in rats.

In the present study, acute hematopoietic toxicity of aniline as a function of time was investigated in rats. The animals were given a single oral dose of aniline hydrochloride (2 mmol/kg) and euthanized at zero (control), 0.25, 0.5, 1, 3, 6, 12, 24 and 48 h following the treatment. The blood methemoglobin level increased dramatically and attained a peak level of 37% (31 fold greater than the controls) at 0.5 h. Thereafter, the increases were less pronounced and the level declined with time. Spleen weight to body weight ratio remained unchanged up to 24 h, but increased approximately 25% at 48 h. Lipid peroxidation (MDA content) in the spleen increased by 39% at 24 h and remained steady even at 48 h. MDA-protein adducts, as quantitated by a competitive ELISA, showed 94, 126 and 265% increases in the spleen homogenates at 12, 24 and 48 h, respectively, following the treatment. However, no changes were observed in the splenic protein oxidation. Morphological examination showed congestion of splenic blood vessels and marked expansion of red pulp at 24 and 48 h. These studies suggest that aniline related changes in the blood are reflected very early as evident from increases in the methemoglobin content, whereas changes in the spleen appear later and are characterized by splenic weight changes, increased lipid peroxidation, MDA-protein adduct formation and morphological changes after a single high dose exposure. The increased lipid peroxidation in the spleen also suggests that free radical-mediated reactions could be the potential mechanism of splenic toxicity of aniline and lipid peroxidation precedes protein oxidation.

Administration, Oral↗
PubMed1997

'Domino' liver transplantation combined with multivisceral transplantation.

Transplantation of the liver contemporaneously with another organ from the same donor is thought to confer an immunologic advantage. The latter is particularly desirable in intestinal transplantation because of the propensity of the intestinal graft to early and late rejections and because in some cases it may facilitate the operation. In clinical practice, shortage of liver grafts constrains liver transplantation to cases in which there is coexisting end stage liver disease.

Adolescent↗
PubMed1997

Oxidative stress in the splenotoxicity of aniline.

Aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia, fibrosis, and a variety of sarcomas in rats. Early biochemical events responsible for the observed effects are not known. To understand the mechanism(s) of aniline-induced splenic toxicity, single and multiple (four and seven) doses of 1 mmol/kg of aniline hydrochloride(AH) were given in rats. Apart from changes in the hematological parameters, these studies demonstrated that AH could induce lipid peroxidation and protein oxidation in the spleen, and significant increases were observed at four doses. Subsequently, a dose-response study of AH was performed. Male SD rats were given four doses each (one dose/day) of 0.25, 0.5, 1, and 2 mmol/kg of AH in water by gavage, while controls received water only. Animals were euthanized 24 hr following the last dose and tissues obtained. Spleen weight increased by 32 and 80% at 1 and 2 mmol/kg doses, respectively. Splenic lipid peroxidation showed dose-dependent increases of 24, 32, and 43% at 0.5, 1, and 2 mmol/kg, respectively. Protein oxidation in the spleen, quantitated by carbonyl content per milligram protein, showed 10, 28, and 27% increases at 0.5, 1, and 2 mmol/kg, respectively. Iron content in the spleen also showed dose-dependent increases of 72, 172, and 325% at 0.5, 1, and 2 mmol/kg, respectively. Dose-related histopathologic expansion of splenic red pulp was characterized by increasing vascular congestion (most pronounced at 2 mmol/kg), increased red pulp cellularity, erythrophagocytosis, and cellular fragmentation at 1 and 2 mmol/kg; iron deposition in red pulp also increased dramatically with dose. These studies establish that aniline induces lipid peroxidation and protein oxidation in the spleen and suggest that oxidative stress plays a role in the splenic toxicity of aniline.

Administration, Oral↗
PubMed1997

Effect of laser treatment on the root canal of human teeth.

The purpose of this study was to examine the morphological and temperature changes of the apical portion of human extracted teeth treated by Nd: YAG, CO2 and Argon-lasers. Seventy-two single-rooted human teeth were studied. The root canals were prepared conventionally. Laser treatment of the apical portion of the canal was carried out by means of an optic fiber or metal tip. Temperatures were recorded thermographically. Two-thirds of the specimens were stained with black India ink and 36% silver ammonium fluoride solution. All specimens were irradiated by the three types of lasers at several intensities and the temperatures were recorded. Half of the specimens were prepared for the telescopic light microscope and for scanning electron microscopic observation, and the rest for histopathological examination by light microscope. The scanning electron microscopic evaluation showed that the laser energy vaporized the deposited debris, producing a glaze-like surface. The histopathological investigation revealed a tapered, enlarged apical lased area. All three laser devices were capable of vaporizing the debris in this way but the degree of morphological change was highly dependent on energy level and duration. The Argon-laser produced the highest temperatures.

Argon↗
PubMed1997

Time-dependent autoimmune response of dichloroacetyl chloride in female MRL +/+ mice.

Welders are exposed to dichloroacetyl chloride (DCAC) when trichloroethene (TCE) is used as a degreasing agent. Human exposure to TCE and tetrachloroethane can also lead to formation of DCAC in situ through metabolism. Due to its strong acylating property, it can bind with cellular macromolecules and act as hapten and consequently may elicit autoimmune (Al) response. Earlier, we reported that both TCE and DCAC induce/accelerate Al response in MRL +/+ mice, and DCAC even at 50 fold lower concentration induced greater Al responses. These studies, however, were conducted at a single time point (six weeks of treatment) and therefore necessitate a time-dependent characterization of this DCAC-induced Al response. Female MRL +/+ were given ip treatments of 0.2 mmol/kg DCAC in 100 microliters of corn oil every 4th day, while controls received an equal volume of corn oil only. DCAC treatment resulted in spleen weight increases at all time points whereas serum IgG showed significant increases at 4, 6 and 8 weeks of treatment. Serum autoantibodies, i.e., antinuclear antibodies, anti-single stranded DNA antibodies and anticardiolipin antibodies showed positive responses only after 4 weeks of treatment. However, the optimal responses were observed at 6 weeks and subsequently the responses diminished (at 8 weeks). The DCAC-specific antibodies showed a pattern similar to autoantibodies, i.e., an optimal response at 6 weeks of treatment. Our results thus suggest that DCAC under the current experimental conditions induces an optimal Al response at 6 weeks of treatment and further emphasize the usefulness of MRL +/+ mice in studying chemical-induced autoimmunity.

Acetates↗
PubMed1997

Donor biliary variations: an overlooked problem?

Documented causes of biliary complications following orthotopic liver transplantation have been related to technical imperfections or insufficient arterial supply. Although anatomical variations of the extrahepatic biliary system are not infrequent, neither their incidence, surgical management nor possible association with complications have been reported in liver transplantation. At our institution, the global incidence of biliary complications following 357 consecutive liver transplants performed in 324 patients over a 2-yr period was 15.4% (55/357). Anomalous donor extrahepatic ducts were verified in 10 cases (2.8%) and they were recognized intraoperatively, prior to biliary reconstruction, in 7 cases. Technical complications occurred in 1 of these 7 and in 3 other cases where the anomalous ducts were not identified until later in the postoperative period when serious clinical problems ensued. We herein present a description of these 10 cases, with reference to the techniques employed to manage the anatomical anomalies and to treat complications. As in any hepatobiliary procedure, awareness of possible variations of the extrahepatic biliary system, intraoperative identification of the anomalous ducts and appropriate tailoring of the surgical technique are advisable in order to avoid serious postoperative complications in liver transplantation.

Adult↗
PubMed1995

Hematopoietic toxicity of linoleic acid anilide: importance of aniline.

The purpose of this study was to investigate the role of hydrolysis products of linoleic acid anilide (LAA), i.e., aniline and linoleic acid (LA), in the toxicity to the hemopoietic system, especially to the spleen. To achieve this, the parent compound (LAA) and its putative hydrolysis products, i.e., aniline or linoleic acid (LA), were given to male SD rats at equimolar doses (0.7 mmol/kg) in 0.25 ml mineral oil by gavage, daily, for 14 days. The controls received equal volumes of vehicle only. Five animals from each group were euthanized at Days 1, 7, and 28 following the last dose. At all time points, spleen weights increased in the LAA- and aniline-treated rats, but spleen to body weight ratios were increased only at Days 1 and 7 in these groups. No changes were observed in the LA-treated rats at any time point. RBC counts were decreased in the LAA and aniline groups at Days 1 and 7, whereas hemoglobin content was decreased by 20 and 13% in the LAA- and aniline-treated rats, respectively, only at Day 1. Methemoglobin content in the LAA and aniline groups also increased by 76 and 101%, respectively, at Day 1. Serum transaminases (AST and ALT) decreased in the LAA, aniline, and LA groups but the decreases were more consistent in the LA group. Serum IgA increased in the LAA and aniline groups only at Day 1. Splenic iron content was increased 381, 486, and 51% in the LAA-treated rats and 474, 491, and 58% in the aniline-treated rats at Days 1, 7, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1995

Iron-induced lipid peroxidation in rat liver is accompanied by preferential induction of glutathione S-transferase 8-8 isozyme.

Since previous studies from this laboratory have suggested that glutathione S-transferase (GST) 8-8 of rat belongs to a distinct subgroup of GST isozymes which may be involved in the detoxification of the products of lipid peroxidation (Zimniak et al., J. Biol. Chem. 269, 992-1000, 1994), during the present studies we examined the effect of iron-induced lipid peroxidation on the expression of GST 8-8 in rat liver. Rats treated with 100 mg/kg body wt iron showed a significant increase in lipid peroxidation in liver. This was accompanied by a concomitant increase in the expression of GST 8-8 in liver as observed in isoelectrophoretic analysis of rat liver GSTs, and an increase in GST activity toward 4-HNE, a toxic product of lipid peroxidation toward which GST 8-8 displays high specific activity. Western blot studies using polyclonal antibodies specifically recognizing GST 8-8 also indicated that, among the GST isozymes of rat liver, GST 8-8 was preferentially induced upon iron treatment. These findings were further confirmed by purifying and quantitating GST 8-8 protein from the controls and iron-treated rats. Significant differences in the specific activities of GST 8-8 purified from the controls and iron-treated rats were observed, indicating that more than one GST isozyme related to GST 8-8 may be present in rat liver. This observation is consistent with the observed heterogeneity in mouse mGSTA4-4 which is an ortholog of rat GST 8-8. Iron treatment also caused significant increase in GSH levels probably because of de novo synthesis as indicated by an increase in gamma-glutamyl cysteine synthetase activity. The results of these studies suggest that GST 8-8, and possibly other related GST isozymes, may play an important role in defense mechanisms against lipid peroxidation.

Aldehydes↗
PubMed1995

Trichloroethene-induced autoimmune response in female MRL +/+ mice.

Trichloroethene (TCE) has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental studies have not been conducted to establish the role of TCE in causing autoimmunity and/or SLE. To clarify the role of TCE in autoimmune responses, subchronic studies were carried out in female autoimmune prone mice (MRL +/+). Three groups of mice (5 weeks old) received intraperitoneal injections of 10 mmol/kg of TCE, 0.2 mmol/kg of dichloroacetyl chloride (DCAC) (one of the metabolites of TCE with strong acylating property), or an equal volume (100 microliters) of corn oil alone (controls). Animals were dosed every 4th day for 6 weeks and euthanized 24 hr following the last dose. Sera and major tissues were collected and analyzed. Spleen weights in the TCE and DCAC groups increased 36% with a similar pattern of change in the spleen-to-body weight ratios. Serum IgG in the TCE and DCAC groups increased 45 and 322%, respectively. Using specific ELISA assays for mice, autoimmune antibodies were detected in the sera of TCE- and DCAC-treated mice in the following patterns: for anti-nuclear antibodies; controls, 0/4; TCE, 4/4; DCAC, 3/5; for anti-ssDNA antibodies; controls, 0/4; TCE, 2/4; DCAC, 5/5; for anti-cardiolipin antibodies; controls, 0/4; TCE, 0/4; DCAC, 3/5. An ELISA developed for the measurement of DCAC-specific antibodies using conjugated DCAC-albumin as an antigen showed the following pattern: for controls, 0/4; TCE, 0/4; DCAC, 5/5. These results suggest that TCE and its metabolite, DCAC, induce and/or accelerate autoimmune responses in female MRL +/+ mice. The greater responses induced by DCAC at a dose 50 times lower than TCE suggests that this metabolite may be important in the mechanisms leading to TCE-induced autoimmunity.

Animals↗
PubMed1995

Fatty acid conjugates of xenobiotics.

In this review, we discuss the formation and toxicity of fatty acid conjugates of xenobiotics. Conjugates formed in vivo and in vitro and those detected as contaminants are reviewed. Due to the lipophilic nature of these conjugates, they may accumulate in various body organs and cause toxic manifestations. In vivo formation of these fatty acid conjugates appears to be catalyzed by enzyme(s). Fatty acid ethyl esters are the most widely studied esters and have been implicated in the onset or pathogenesis of myocardial and pancreatic diseases in alcoholics. In experimental animals, studies on 2-chloroethyl linoleate, palmitoylpentachlorophenol and oleoyl and linoleoyl anilides clearly indicate that lipid conjugates of xenobiotics are involved in target organ toxicity. These findings warrant further detailed studies to isolate and identify other fatty acid conjugates and to evaluate their toxicity. Thorough toxicokinetic and metabolic studies are also needed to identify putative toxic agents. Identifying these agents could help in understanding the mechanism of pathogenesis associated with lipid conjugation. Finally fatty acid conjugates of drugs (prodrugs), have been shown to have increased half-lives and long-lasting dose-response. Thus these conjugates may be useful for enhancing the therapeutic potential of drugs and should be explored further.

Animals↗