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Biomedical subjects

M Saleem

Publications and source records attributed to M Saleem.

At least 73 records · Page 4Linked to original sources

Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in murine skin.

In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents, which could be useful for the human population. Tephrosia purpurea has been shown to possess significant activity against hepatotoxicity, pharmacological and physiological disorders. Earlier we showed that Tephrosia purpurea inhibits benzoyl peroxide-mediated cutaneous oxidative stress and toxicity. In the present study, we therefore assessed the effect of Tephrosia purpurea on 12-O-tetradecanoyl phorbal-13-acetate (TPA; a well-known phorbol ester) induced cutaneous oxidative stress and toxicity in murine skin. The pre-treatment of Swiss albino mice with Tephrosia purpurea prior to application of croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous carcinogenesis. Skin tumor initiation was achieved by a single topical application of 7,12-dimethyl benz(a)anthracene (DMBA) (25 microg per animal per 0.2 ml acetone) to mice. Ten days later tumor promotion was started by twice weekly topical application of croton oil (0.5% per animal per 0.2 ml acetone, v /v). Topical application of Tephrosia purpurea 1 h prior to each application of croton oil (phorbol ester) resulted in a significant protection against cutaneous carcinogenesis in a dose-dependent manner. The animals pre-treated with Tephrosia purpurea showed a decrease in both tumor incidence and tumor yield as compared to the croton oil (phorbol ester)-treated control group. In addition, a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation was also observed in animals pre-treated with a topical application of Tephrosia purpurea. The effect of topical application of Tephrosia purpurea on TPA-mediated depletion in the level of enzymatic and non-enzymatic molecules in skin was also evaluated and it was observed that topical application of Tephrosia purpurea prior to TPA resulted in the significant recovery of TPA-mediated depletion in the level of these molecules, namely glutathione, glutathione S-transferase, glutathione reductase and catalase. From these data we suggest that Tephrosia purpurea can abrogate the tumor-promoting effect of croton oil (phorbol ester) in murine skin.

9,10-Dimethyl-1,2-benzanthracene↗

Haplophytin-A and B: the alkaloidal constituents of Haplophyllum acutifolium.

During the phytochemical investigation of Haplophyllum acutifolium, two alkaloids named haplophytin-A (1) and B (2) have been obtained. In addition, some known constituents: flindersine (3), kusunokinin (4), beta-sitosterol, oleanolic acid, cholesterol and hexadecanoic acid, have also been obtained. The known constituents have never been obtained from this source. The structures of all the isolated constituents were elucidated by spectroscopic means. However, the structures of constituents 1 and 2 were further confirmed through HMBC technique.

Alkaloids↗

Seasonal variations in the microbial population density present in biological sludge.

Sludge produced during the treatment of wastewater is being used as fertilizer in several Gulf countries. The Water and Sewage Authority of Saudi Arabia has targeted the reuse of the total amount of sludge in the future. However, these sludges should be properly treated before reuse as they contain a large number of pathogens and parasites. Little information is available on the microbial characteristics of sludge produced in wastewater treatment plants operating in this region. Variations in the population densities measured by Standard Plate Count, total coliform, fecal coliform, coliphage, and Clostridium perfringens present in the sludge, were monitored during a one year study at Al-Khobar wastewater treatment plant so that the effect of seasonal variations on the fate of these five indicator microorganisms could be investigated. This paper covers an evaluation of the fate of indicator microorganisms in the drying sludge. Insight gained in this study will be helpful in establishing guidelines for the use of sludge as fertilizer for agriculture purposes.

Clostridium perfringens↗

Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II.

Biological Evolution↗

Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats.

In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.

Animals↗

Measurements of the mass, total width, and two-photon partial width of the eta(c) meson.

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.

Journal Article↗

Immobilization of antibodies on alginate-chitosan beads.

An anti-hapten IgG was covalently immobilized on glutaraldehyde-activated alginate-chitosan gel beads. The antibody immobilization efficiency was influenced by glutaraldehyde-bead reaction time, IgG concentration and pH. In addition, immobilization conditions such as glutaraldehyde and antibody concentrations influenced antibody hapten binding affinity. The immobilized IgG on the beads was stable and no reduction in the percent binding to hapten was noticed following 25 days of storage. It was concluded that antibodies could be successfully immobilized on alginate-chitosan gel beads. Such a system can be applied for the development of immunoaffinity purification and immunoassays.

Alginates↗

Chemistry of Zataria multiflora (Lamiaceae).

The hexane soluble part of Zataria multiflora afforded three new aromatic constituents which include two p-cymene derivatives: multiflotriol (1), multiflorol (2) and an aromatic ester of p-hydroxy benzoic acid (3). In addition to these three new compounds, three known compounds, dihydroxyaromadendrane, luteolin and alpha-tocopherolquinone, have also been isolated for the first time from the same source. The structures of all the isolated constituents were elucidated by means of spectroscopic methods including 2D-NMR techniques.

Flavonoids↗

Attenuation of benzoyl peroxide-mediated cutaneous oxidative stress and hyperproliferative response by the prophylactic treatment of mice with spearmint (Mentha spicata).

The modulating effect of spearmint (Mentha spicata) on benzoyl peroxide-induced responses of tumor promotion in murine skin was investigated. Benzoyl peroxide (BPO) is an effective cutaneous tumor promoter acting through the generation of oxidative stress, induction of ornithine decarboxylase activity and by enhancing DNA synthesis. BPO treatment (20 mg/animal) increased cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, was decreased and the level of cutaneous glutathione was depleted. BPO treatment also induced the ornithine decarboxylase activity and enhanced the [3H]thymidine uptake in DNA synthesis in murine skin. Prophylactic treatment of mice with spearmint extract (10, 15 and 20 mg/kg) 1 hr before BPO treatment resulted in the diminution of BPO-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P < 0.05 ). In addition, depleted levels of glutathione, inhibited activity of glutathione dependent and antioxidant enzymes were recovered to a significant level (P < 0.01, P < 0.05 and P < 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis was inhibited significantly (P < 0.05 ) in a dose-dependent manner. The protective effect of spearmint was dose dependent in all parameters. The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice.

Animals↗

Two new diterpenoids from Salvia triloba.

Two new diterpenoids, trilobic acid (1) and trilobiol (2), have been isolated from the methanolic extract of Salvia triloba. Their structures were elucidated with the aid of NMR spectroscopy including two-dimensional-NMR techniques.

Diterpenes↗

Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress.

The hepatoprotective activity of the 50% ethanol extract of the bark of Lawsonia alba syn. L. inermis was investigated against the carbon tetrachloride-induced oxidative stress. Pretreatment of rats with doses of 250 and 500 mg/kg of the plant extract significantly (P < 0.001) lowered serum transaminases (GOT and GPT) and LDH levels, respectively, in a dose dependent manner against the significant (P < 0.001) rise of these damage marker enzymes when challenged with CCl4 (1 ml/kg, orally). Parallel to these changes, the plant extract prevented CCl4-induced oxidative stress by significantly maintaining the levels of reduced glutathione (GSH), its metabolizing enzymes and simultaneously inhibiting the production of free radicals. Pretreatment of rats with the extract also inhibited the peroxidation of microsomal lipids in a dose-dependent manner.

Animals↗

Early stage carcinoma of oral tongue: prognostic factors for local control and survival.

The purpose of this study was to assess prognostic factors, treatment outcomes and patterns of relapse in patients with early stage (T1-2 N0) squamous cell carcinoma of oral tongue treated primarily by surgery. The medical records of all patients with early stage (T1-2 N0) oral tongue cancer, radically treated at King Faisal Specialist Hospital and Research Center between January 1980 and December 1997, were reviewed. Eighty-five patients were identified for analysis, 38 male and 47 female. With a median follow-up for surviving patients of 64 months, 5-year actuarial overall, disease-specific (DSS), and relapse-free survival (RFS) were 71, 75, and 63%, respectively. Univariate analysis for DSS showed survival advantage for patients with tumor thickness (TT) of < or =10 mm (P=0.0002) and distance from resection margin (DFRM) of > 5 mm (P=0.005). The effect of TT of < or =10 mm was maintained (P=0.001) on multivariate analysis. Higher RFS was observed with TT of < or =10 mm (P=0.0002), DFRM of > 5 mm (P=0.0002) and DFRM of >10 mm (P=0.007). On multivariate analysis higher RFS was also found for TT < or =10 mm (P=0.01) and DFRM >5 mm (P=0.01). Salvage of local tongue recurrence was higher than neck node failure, with 5-year DSS of 71 and 19%, respectively (P=0.007). Time interval for recurrence showed no significant impact on outcome. In T1-2 N0 oral tongue cancer, TT, and DFRM are significant prognostic factors for both local control and survival. Neck node recurrence is associated with poor prognosis and low salvage rate.

Adult↗

ACTH-producing pituitary cancer: experience at the King Faisal Specialist Hospital & Research Centre.

Pituitary gland is an uncommon site of a primary cancer. Of more than 600 cases of pituitary tumors seen at the KFSH&RC between 1975 to 1998 only 3 patients had primary pituitary cancer. We have previously reported a case of pituitary fibrosarcoma arising as a rare complication of external radiotherapy (ERT) for GH-secreting pituitary adenoma (PA) [1]. We report now 2 cases of ACTH-producing primary pituitary carcinoma (ACTH-PPC); their follow-up data provide information on the natural history of this cancer. Patient #1; a 46 year old lady with Cushing's disease (CD) presented with an enlarged right cervical lymph node (LN) 2 years after having undergone a partial hypophysectomy through transsphenoidal surgery (PHYPX/TSS) and ERT for an invasive pituitary tumor. Patient #2; a 26 year old man presented with CD and underwent bilateral adrenalectomy (ADx) and pituitary ERT. Thirty-nine months later he developed Nelson's syndrome and a PHYPX/TSS was performed. Incidentally discovered hepatic metastases in this patient and an excisional biopsy of the LN in patient #1 showed histological features very similar to the pituitary tumor, and they stained strongly positive for ACTH. Perinuclear spherical hyalinized cytoplasmic inclusions were seen in the LN biopsy that corresponded to bundles of type 1 microfilaments (specific for pituitary ACTH-producing cells) seen by electron microscopy. A whole body 18-Fluoro-2-Deoxy-D-Glucose positron emission (FDG-PET) scanning, showed an intense uptake in the neck mass. A trial of octreotide did not change the exceedingly high levels of ACTH in patient #2, further supporting the diagnosis of ACTH-PPC. The clinical course of 102 months prior to his demise showed continued progression of the primary and the metastatic tumor. Patient #1, is alive at 15 months follow-up; hypercortisolemia is controlled using ketoconazole. ACTH-PPC should be entertained in a patient with CD presenting with persistent cervical lymphadenopathy. The clinical course in our patients suggests that the emergence of PC may involve a proliferative continuum from a pre-existing PA to an invasive tumor, culminating in a carcinoma. Adjunctive events such as ERT/ADx may predispose to the evolution of PC in genetically susceptible individuals. Because ERT is an effective treatment for PA its use will continue; it is important to be aware of the possible complication of primary pituitary carcinoma.

Adrenocorticotropic Hormone↗

Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice.

In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in mice. Cumene hydroperoxide treatment at a dose level of 30 mg/animal/0.2 ml acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed. Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of cumene hydroperoxide (30 mg/animal/0.2 ml acetone) treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (P<0.05). In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (P<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating cumene hydroperoxide-induced cutaneous oxidative stress and toxicity.

Animals↗

Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors.

AIM: To identify the prognostic significance of different factors in patients with squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Seventy-seven patients with carcinoma of the tongue were treated radically at the King Faisal Specialist Hospital and Research Centre between 1980 and 1989. Twenty patients (26%) were treated by resection alone, 11 (14%) with radiotherapy alone, and 46 (60%) with combined resection and radiotherapy. RESULTS: Forty-seven patients (61%) had T(1-2), 28 (36%) T(3-4), and two T(x) tumours. The regional nodes were clear in 53 (69%) and contained metastases in 24 patients (31%). Thirty patients (39%) developed recurrences, which were local in 9, regional in 14, locoregional in 5, and locoregional with metastatic disease in 2. The five and 10-year overall actuarial survival for all patients were 65% and 53%, respectively, and the corresponding relapse-free survival 56% and 50%. Univariate and multivariate analyses were done of seven variables - age (<40 compared with >/=40 years), sex, chewing tobacco use, smoking, TNM stage, surgical margins (clear or invaded), and treatment (resection, radiotherapy, or the combination). On univariate analysis chewing tobacco (P=0.04), smoking (P=0.01), invaded resection margins (P=0.04), involved regional lymph nodes (P=0.009), T4 tumours, and patients treated with radiotherapy alone (P=0.001) were associated with poor overall survival. Factors associated with shorter relapse-free survival were age >40 (P=0.03), chewing tobacco (P=0.04), invaded resection margins (P=0.01), and smoking (P=0.01). On multivariate analysis, invaded resection margins and smoking (P=0.04)(P=0.02) were associated with shorter overall survival and relapse-free survival (P=0.03 and (P=0.01), while chewing tobacco independently influenced relapse-free survival only (P=0.03). CONCLUSION: Invaded resection margins and smoking were the only independent prognostic factors that affected both overall and relapse-free survival. Those who chewed tobacco were at high risk of locoregional failure.

Adult↗

F-18 fluorodeoxyglucose chest uptake in lung inflammation and infection.

PURPOSE: F-18 fluorodeoxyglucose (FDG) may accumulate at sites of inflammation or infection, making interpretation of whole-body scans difficult in patients with cancer. METHODS: More than 650 whole-body positron emission tomographic (PET) scans performed to examine patients with cancer were reviewed to identify uptake in pulmonary infection or inflammation based on the appearance of F-18 FDG chest uptake, chest radiographs, computed tomography, or all of these. RESULTS: Ten patients had uptake in benign lung disease. Eight patients had head and neck tumors and two patients had breast cancer. Intense focal or multifocal F-18 FDG chest uptake was seen in 6 of 10 scans. This was difficult to distinguish from pulmonary metastases based on the scan appearance. However, in the remaining patients, the uptake was atypical for malignancy and displayed an apical, segmental, or lobar pattern. In all patients, the F-18 FDG lung uptake corresponded to benign radiologic changes (infiltration, consolidation, or atelectasis), and the final diagnosis was pulmonary inflammation or infection. Nine patients were asymptomatic and one patient had clinical aspiration pneumonia. Follow-up PET scans were performed in five patients to evaluate their conditions. Chest uptake disappeared completely in three patients and partially in two patients, and there were no new findings. Variable degrees of F-18 FDG chest uptake have been reported with more than 40 different benign causes. They can be classified based on the underlying mechanism into four major categories: 1) Inflammation or infection, 2) benign tumor, 3) physiologic activity, and 4) iatrogenic. Most of these false-positive cases are included in the first category. CONCLUSIONS: Pulmonary infection or inflammation might predispose patients to localized F-18 FDG chest uptake mimicking pulmonary metastases and limiting the specificity of whole-body scans performed in patients with cancer.

Adult↗