Biomedical subjects

S Rodriguez

Publications and source records attributed to S Rodriguez.

At least 37 records · Page 2Linked to original sources

PubMed2001

Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.

PURPOSE: To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS: Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS: Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION: The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

Antineoplastic Agents↗

PubMed2001

Sampling variance and distribution of the D' measure of overall gametic disequilibrium between multiallelic loci.

The development of the theory of estimation of gametic disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of Dhat' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of Dhat' was investigated under different scenarios of disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of Dhat', conditioned on the sample size, number of alleles and their frequencies, and disequilibrium components. It was found that the sampling distribution of Dhat' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall disequilibrium, which is relevant to evaluate disequilibrium between multiallelic loci in populations.

Alleles↗

PubMed2001

Strain difference (WKY, SPRD) in the hepatic antioxidant status in rat and effect of hypertension (SHR, DOCA). Ex vivo and in vitro data.

We assessed the hepatic antioxidant status of spontaneously (SHR) and desoxicorticosterone acetate (DOCA)-induced hypertensive rats and that of respective normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For this we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) content, glutathione-related enzyme (peroxidase, reductase and transferase) activities as well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant status and the cytotoxicity of acetaminophen, a radical- and hydrogen peroxide-mediated hepatotoxic compound, were also assessed in vitro in cultured hepatocytes isolated from hypertensive (SHR, DOCA) and normotensive control (WKY, SPRD) rats. Our results suggest that a difference exists in the hepatic antioxidant status between rat strains, with GSH levels being lower (-15%) and lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte cultures from WKY rats, both GSH content and catalase activity were lower (-30 and -70% respectively) compared to hepatocyte cultures from SPRD rats. This was associated with a 35% higher cytotoxicity of acetaminophen in cultured hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats. Hypertension in DOCA rats (mmHg: 221+/-9 vs. 138+/-5 in control SPRD rats) was associated with decreases (about 30%) in both glutathione peroxidase (GSH-Px) and catalase activities, ex vivo in livers and in vitro in hepatocyte cultures. Hypertension in SHR (mmHg: 189+/-7 vs. 130+/-5 in control WKY rats) was also associated with decreases (about 50%) in GSH-Px activity, ex vivo in livers and in vitro in hepatocyte cultures but catalase activity was not modified. The IC50 of acetaminophen was also lower in hepatocytes from hypertensive rats compared to respective controls, which could be related to the weakened antioxidant status in hepatocytes from hypertensive rats. Our data thus suggest that hepatocyte cultures are appropriated tools in which to assess hepatotoxicity and hepatoprotection in hypertension.

Acetaminophen↗

PubMed2001

Short report: transient antibody response in Taenia solium infection in field conditions-a major contributor to high seroprevalence.

The discordance between extremely high seroprevalence of Taenia solium antibodies in disease-endemic populations, relatively few symptomatic cases of neurocysticercosis, and high background levels of putatively inactive brain lesions (mainly calcifications) in seronegative controls have confused researchers, clinicians, and epidemiologists in the last decade. We reviewed longitudinal serologic data from general population serosurveys in 3 different disease-endemic areas of Peru and Colombia and found that approximately 40% of seropositive people were seronegative when resampled after 1 year (3 surveys) or after 3 years (1 survey). Transient antibodies may have significant implications for the epidemiology of and immunity to this disease.

Animals↗

PubMed2001

Antimitotic actions of a novel analog of the fungal metabolite palmarumycin CP1.

The pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities but their antineoplastic effects are not well established. We have examined their antiproliferative actions against tumor cells using a temperature-sensitive tsFT210 mouse mammary carcinoma cell line and found that a novel palmarumycin analog, [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4-spiro-2'-naphtho[1",8"-de][1',3'][dioxin] or SR-7, prominently blocked mammalian cell cycle transition in G2/M but not in G1 phase. We found no evidence for inhibition of the critical mitosis-controlling cyclin-dependent kinase Cdk1, or its regulator, the dual specificity phosphatase Cdc25. Moreover, Cdk1 was hypophosphorylated and not directly inhibited by SR-7. SR-7 also failed in vitro to hypernucleate bovine tubulin, did not compete with colchicine for tubulin binding, and only modestly blocked GTP-induced assembly. In addition, SR-7 caused almost equal inhibition of paclitaxel-sensitive and -resistant cell growth. Moreover, unlike benchmark tubulin-disrupting agents, SR-7 did not cause hyperphosphorylation of the antiapoptotic protein Bcl-2. Thus, SR-7 represents a novel chemical structure that can inhibit G2/M transition by a mechanism that appears to be independent of marked tubulin disruption.

Animals↗

PubMed2001

Management of ischemic hemorrhagic cystitis with hyperbaric oxygen therapy.

We report a case of a T8 paraplegic woman who experienced necrosis of the bladder due to inadvertent chronic over distention. After bladder repair, the patient suffered from severe ischemic hemorrhagic cystitis. Despite many attempts to control the bleeding with standard treatments, the hematuria continued. Although hyperbaric oxygen (HBO2) therapy has not been proven to be helpful in patients with hemorrhagic cystitis not related to radiation or chemotherapy, the physiopathologic mechanisms of the cysttis, involving ischemia, led us to believe that outpatient would benefit from HBO2 therapy in analogy to the approved use of HBO2 therapy in radiation cystitis. Since the use of HBO2 therapy has not been previously reported in this situation, we met with some hesitation from the HBO2 therapy department After reviewing the literature and discussing the case, a medical panel reached a consensus to allow us to commence the treatment The patient had a remarkable response, and remains without hematuria 6 mo. after treatment.

Cystitis↗

PubMed2000

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Adult↗

PubMed2000

Direct evidence of a radical mechanism in the addition reaction of iododifluoroesters to olefins by spin trapping

We present EPR analysis of the reaction of ethyl iododifluoroacetate with 1-tetradecene in the presence of Zn + NiCl2 x 6H2O, confirming the mechanistic studies that provide evidence of a single electron transfer process. We have trapped for the first time the ethoxycarbonyldifluoromethyl radical with a variety of spin traps, such as phenyl tert-butyl nitrone (PBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), 2-methyl-2-nitrosopropane (MNP), and 2-nitro-2-nitrosopropane (NNP), and the EPR spectra of the corresponding adducts have been recorded. In a second step the ethoxycarbonyldifluoromethyl radical adds to the olefin to furnish a second radical intermediate, which can be trapped with NNP. Evidence of this second radical was obtained by EPR only with electron-rich olefins, such as alpha-methylstyrene and 2,4,6-trimethylstyrene, and the new adducts were recorded and interpreted. In addition, we also report the EPR spectra of the corresponding adducts when other alkylating reagents are used, such as ethyl iodoacetate, n-perfluorohexyl iodide, methyl omega-iodohexadecanoate, and n-butyl iodide.

Journal Article↗

PubMed2000

Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA-salt hypertensive male Sprague Dawley rats.

The effects of DOCA-salt hypertensive treatment on hepatic glutathione-dependent defense system, antioxidant enzymes, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities were investigated in male Sprague Dawley rats. Compared with controls, DOCA-salt hypertensive rats had lower body weights (linked to liver hypertrophy). Mixed function oxidase and p-nitrophenol-UGT activities were not affected by the treatment but a significant lower rate of the glucuronoconjugation rate of bilirubin (p < 0.001) was observed in DOCA-salt hypertensive rats. While cytosolic glutathione contents and glutathione reductase activity were not affected, glutathione peroxidase (p < 0.001), glutathione transferase (p < 0.001) and catalase (p < 0.01) activities were decreased and associated with higher malondialdehyde contents (p < 0.001) in treated rats. The imbalance in liver antioxidant status (increasing generation of cellular radical species), associated with increases in lipid peroxidation, suggests that oxidative stress might be directly related to arterial hypertension in DOCA-salt treated male Sprague Dawley rats.

Animals↗

PubMed2000

Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague Dawley rats--relation with liver antioxidant status.

The effects of 8-week diethylmaleate (DEM) and clofibric acid (CFA) supplemented diet on blood pressure, body and liver weights, liver antioxidant status and nitric oxide synthase (NOS) activity were investigated in 8-week DOCA-salt treated and untreated Sprague-Dawley male rats. It appeared that DEM and particularly CFA treatments were associated with a significant decrease in blood pressure in DOCA-salt treated rats, and an accentuation of the decreases in body weights in both diet supplemented groups. This was not associated with increases in NO production in the liver. In contrast, hepatic lipid peroxidation was significantly decreased in both DOCA-salt treated and untreated groups on DEM and particularly on CFA supplemented diet. The protective effects of CFA and DEM against hepatic cellular damage could be involved in the decreases in blood pressure in DOCA-salt treated rats, where CFA was more efficient than DEM. In CFA supplemented groups, there was a strong increase in hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), and catalase (CAT) activities and in DEM supplemented groups, increases in SOD and CAT activities and in GSH levels were observed. Our data suggest that normalization of blood pressure in DOCA-salt treated rats by CFA was due to an enhancement of the half-life of NO while DEM increased its availability.

Animals↗

PubMed2000

Increased arginase activity in aorta of mineralocorticoid-salt hypertensive rats.

The present study was designed, first to investigate aortic arginase activity during the development and the establishment of mineralocorticoid-salt (DOCA-salt) hypertension, and second, to determine the relationship between arginase activity and blood pressure by giving a protein-supplemented diet (50% casein) known to increase hepatic arginase activity. Our results showed that aortic arginase activity in established hypertension of DOCA-salt rats was higher than in normotensive rats. The protein-supplemented diet (50% casein) accelerated the development of DOCA-salt hypertension. There was a positive correlation between arginase activity and the level of blood pressure in these DOCA-salt hypertensive rats fed 50% casein but not in DOCA-salt hypertensive rats on a normal (20% casein) diet. In normotensive rats, the protein-supplemented diet decreased aortic arginase activity and produced no change in systolic blood pressure. Our data suggest that aortic arginase activity is modified in established DOCA-salt hypertension and could participate in the physiopathology of arterial hypertension.

Animals↗

PubMed1999

Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development?

Recent work has shown the expression of Neurotrophins low (p75) and high affinity (Trk's A, B, and C) receptors in the developing inner ear sensory neurons of chick and mouse. Likewise the biological significance of such receptor expression was demonstrated by using both Trks and Neurotrophins null mutant mice. The present study was conducted to determine the expression of Trks and p75 proteins in the human inner ear throughout development. Hence to assess the potential role of Neurotrophins in the development of auditory and vestibular specific innervation in man. In other words, we intend to address the issue whether or not what null mutant mice for Trks and p75 have revealed on inner ear development may be relevant for human embryos. Fifty-two inner ears and their cochleovestibular ganglions (CVG) from human embryos and fetuses, ranging from 5 to 24 weeks of pregnancy were analyzed. Both Western blot and immunocytochemistry on frozen sections were used as complementary procedures. Quantitative Western blot studies revealed that Trk-B and C immunoreactivity (IR) appeared by embryonic week 5 in CVG neurons, increased at high levels between embryonic weeks 7 and 12, and later on, in 15 week-old specimens and older began to decrease to minimal levels. Trk-A IR was detected at just moderate levels during 5 and 7 weeks reflecting the presence of NGF high affinity receptors only at these earlier developmental ages. The p75 IR was detected at high degrees in the early stage of the 5th week and at abundant levels in all studied inner ears from the 7th to the 24th pregnancy week. These Western blot observations were corroborated by immunocytochemistry on frozen sections, which also revealed a major distribution of both p75 and Trks on neuronal bodies while p75 appears localized on supporting cells. Our findings reveal a tight correlation between p75 and Trks expression throughout human development and specific inner ear developmental events, such as target-dependent neuronal cell death and afferent hair cells innervation. That kind of association of p75 and Trks temporal pattern with distinctive steps in inner ear developmental schedule, is a feature shared between human embryos and other mammals, such as mouse. Based on the present results and considering them together with the reported phenotype of p75 and Trks null mutant mice, we hypothesize that p75 and Trk receptors, as well as, their binding Neurotrophins may be essential in human inner ear development. Accordingly, they may be required molecules for sensory epitheliums innervation and target-dependent neuronal cell death, during embryogenesis and even early postnatal life, in man.

Animals↗

PubMed1999

Infusion phlebitis in patients with acute pneumonia: a prospective study.

STUDY OBJECTIVES: To prospectively assess the relative risk for phlebitis in a series of consecutive patients with pneumonia and to identify risk factors that predict an increased risk for phlebitis. SETTING: Internal medicine department of a tertiary teaching hospital. PATIENTS: Seven hundred sixty-six consecutive patients with acute pneumonia receiving IV therapy. INTERVENTIONS: Only the first catheter was taken into account. There were 308 short lines (a 51-mm, 18-gauge Teflon catheter); 307 midsized lines (a 28-cm, 16-gauge polyvinyl chloride catheter); and 151 long lines (71-cm, 14-gauge plain polyurethane catheter). Eighteen variables were prospectively evaluated in an open, nonrandomized study for their contribution to the occurrence of phlebitis. RESULTS: The overall phlebitis rate was 39%. Phlebitis developed in 53% of patients with short lines, in 41% of patients with midsized lines, and in 10% of patients with long lines, and these catheters remained in place an average (+/- SD) of 3.0+/-2.4 days, 4.6+/-3.4 days, and 7.8+/-6.6 days, respectively. The variables that influenced the development of phlebitis, as determined by multivariate analysis, were the following: type of catheter; blood hemoglobin levels; and IV therapy with either corticosteroids or erythromycin. CONCLUSIONS: According to our data, when the use of a catheter is expected to be required for < or = 36 h, a short line can be used. If a longer duration is expected, a longer line is warranted. Ours is the first study in which the relationship between blood hemoglobin levels and phlebitis has been reported. Because the use of intravascular devices is increasingly common, a more complete knowledge of the factors that influence their acceptance has become essential.

Acute Disease↗

PubMed1998

Ambulatory management of varicella-zoster virus infection in immunocompromised cancer patients.

Immunocompromised patients with varicella-zoster virus (VZV) infection are at greater risk for dissemination and the development of complications than immunocompetent individuals. Consequently, they are generally hospitalized in strict isolation rooms and treated with parenterally administered acyclovir. Although effective, this approach is expensive and creates logistic difficulties in the hospital. We treated 38 immunosuppressed cancer patients presenting to our ambulatory treatment center with VZV infections with intravenous acyclovir (500 mg/m2 8-hourly) in an ambulatory/home setting. Patients were monitored for success or failure of therapy, progression of infection, development of complications or drug toxicity, and satisfaction/compliance with therapy. Most patients (33, or 87%) responded to therapy. Among the failures, 2 patients had progressive VZV infection, 2 were hospitalized due to renal toxicity, and 1 developed a superinfection. All patients eventually responded and there were no deaths on this study. Two patients relapsed within 1 month of initial response. Both responded to retreatment with acyclovir, without hospitalization. The median duration of parenteral therapy with acyclovir was 7.5 days. Seven patients (18%) had to be switched to oral acyclovir (800 mg, 5 times a day) before complete response, owing to problems with venous access. All 7 completed therapy successfully. Overall, patients expressed a high level of satisfaction with outpatient therapy, and there were no instances of noncompliance or patient requests for withdrawal from study. The results of this study indicate that VZV infections in clinically stable immunosuppressed cancer patients are relatively benign and do not require hospitalization. Parenterally administered acyclovir in an ambulatory setting is effective therapy for such infections.

Acyclovir↗

PubMed1998

Meal type affects heartburn severity.

This study compared heartburn severity, number of episodes, and changes in esophageal pH induced by three meals. Symptomatic volunteers consumed the following on different occasions: McDonald's Quarter Pounder, french fries, and chocolate shake; McDonald's Sausage Biscuit with Egg, cheese, raw onion, and chocolate milk; and Wendy's Chili and red wine. Increases in reflux episodes over baseline for the hamburger, sausage biscuit, and chili meals were 28.8 +/- 5.7, 36 +/- 5.5 and 43.7 +/- 8.8, respectively. The sausage biscuit and chili increased reflux compared to the hamburger (P < 0.05), but the chili did not differ statistically from the sausage biscuit meal. Onset and peak heartburn for the hamburger, sausage biscuit, and chili meals were 45 and 90, 30 and 120, and 15 and 150 min, respectively. Despite lower fat content, chili and red wine promoted more reflux and heartburn pain than the other meals, demonstrating the importance of meal selection in provocative meal studies.

Cross-Over Studies↗

PubMed1997

Pulmonary infections mimicking cancer: a retrospective, three-year review.

Pulmonary infections can mimic or occasionally co-exist with pulmonary neoplasms. In order to determine the frequency and nature of these infections, we conducted a retrospective analysis, covering a 3-year period, of patients who were referred to our center with presumed lung cancer but turned out to have pulmonary infection instead. The overwhelming majority of patients (93.3%) referred to "rule out" lung cancer were documented as having a neoplastic process, and only 1.3% had an infection. Fungal infections (histoplasmosis, cryptococcosis, coccidiomycosis) accounted for 46%, mycobacteria for 27%, bacteria for 22%, and parasitic lesions (dirofilariasis) for 5% of these infections. The most common clinical manifestations were cough and chest pain, and the most common radiographic finding was a solitary pulmonary nodule. There were no specific clinical or radiographic features predictive of either infection or neoplastic disease. All patients responded to specific anti-infective therapy with or without surgical excision. Our data indicate that pulmonary infections mimic neoplasms very infrequently. However, establishing a specific diagnosis is critical, since the management and outcome of these two processes are entirely different.

Adolescent↗

PubMed1997

Expression of the cytoskeletal protein MAP5 and its regulation by neurotrophin 3 (NT3) in the inner ear sensory neurons.

Microtubule-associated proteins (MAPs) are essential cytoskeletal components during development for neurogenesis and neuronal plasticity. Inner ear innervation is accomplished by cochleovestibular ganglion (CVG) neurons in a highly specific, well-defined pattern, which is regulated by neurotrophic factors belonging to the neurotrophin family. The inner ear offers a suitable model for studying the expression of MAPs and assessing their role in neurotrophin-induced effects that are required for neuron-target innervation. The present study was undertaken to analyze the expression and localization of MAP5 isoforms during development of CVG neurons in vivo an in vitro; as well as the regulation of MAP5 by neurotrophin-3 (NT3) in cell culture. MAP5 expression in the inner ear of chick embryos and postnatal specimens was monitored using immunoblots and immunohistochemistry on frozen sections. MAP5 was highly expressed during the early stages of CVG development, at embryonic day (E)4, being located in both neuronal perikarya and neurites. Expression was maintained during the neurite outgrowth phase (E6-E12), when strong MAP5 immunostaining was observed at the same cellular locations. MAP5 expression decreased suddenly at E14, after the establishment of specific connections between the CVG neurons and their targets, the sensory epithelium of the inner ear. In cultured CVG neurons addition of NT3 led to increased MAP5 expression and produced neurite outgrowth. Both effects are differentially regulated in parallel by low (0.5 ng/ml) and high (5 ng/ml) NT3 concentrations. Present results suggest that MAP5 may be involved in neurotrophin-induced microtubule bundling during neurite outgrowth of auditory neurons.

Age Factors↗

PubMed1997

A histopathological study of liver and kidney in male Wistar rats treated with subtoxic doses of t-butyl alcohol and trichloroacetic acid.

Tertiary butyl alcohol and trichloroacetic acid are known to be contaminants in drinking water. In order to evaluate the interactive toxicity of t-butyl alcohol with trichloroacetic acid, young male Wistar rats were dosed through water at a dose level of t-butyl alcohol (TBA)-0.5% (v/v), trichloroacetic acid (TCA)-25 ppm and a combined dose of TBA + TCA (0.5% v/v TBA-25 ppm TCA) for a period of 10 weeks ad libitum and were maintained on normal diet. The control animals received plain water and normal diet. The liver and kidney histology was undertaken to see whether subtoxic administration of TBA and TCA individually as well as combined administration for a period of 10 weeks would bring about any histological alterations. It was observed that TBA, TCA and TBA + TCA caused histological alterations in the liver such as centrilobular necrosis, vacuolation in hepatocytes and loss of hepatic architecture. TBA and TBA + TCA caused periportal proliferation and lymphocytic infiltration. Hypertrophy of hepatocytes in the periportal area was a characteristic feature in the liver of TCA treated rats. Moreover, in the histology of the kidney, in the three treated groups, degeneration of renal tubules, with syncitial arrangements of the nucleus of renal tubular epithelial cells was evident. In addition to this, degeneration of the basement membrane of the Bowmans capsule, diffused glomeruli and vacuolation of glomeruli was also evident in the three treated rat kidneys. Renal tubular proliferation in certain areas was also evident in certain areas of the kidney in TCA treated rats. The results indicate that, TBA and TCA do bring about alterations in histology of liver and kidney, but on combined administration, do not show enhanced toxicity in the form of increased hepatic and renal injury.

Animals↗