Effects of pharmacogenetics on pharmacokinetics and toxicity of doxorubicin in Egyptian breast cancer patients.

This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients with breast cancer.Patients administered DOX (60 mg/m2) for 4 cycles every 3 weeks. The peak DOX plasma concentration was measured using a validated chromatographic method. The genotyping for the selected SNPs, SLC22A16 T > C (rs714368), and CBR1 C > T (rs20572), was performed by RT-PCR. Patients were monitored for hematological and cardiac toxicities.The variant carriers of CBR1 C > T (rs20572) exhibited significantly higher DOX concentration, but no significant association to DOX-induced hematological toxicity. On the other hand, SLC22A16 T > C (rs714368) had no significant influence on DOX plasma concentration, but was significantly correlated with lower risk of neutropenia (OR 0.31, 95% CI 0.12-0.75, p = 0.01) and leukopoenia (OR 0.18, 95% CI 0.07-0.5, p = 0.001). DOX-related cardiotoxicity was correlated with the cumulative dose of DOX (R = 0.238, p = 0.017), but not with any of the two examined SNPs.Genetic polymorphisms in SLC22A16 and CBR1 may explain the inter-individual variations in DOX pharmacokinetics and toxicity. Using pharmacogenetic testing is important to customise drug therapy for cancer patients treated with anthracyclines.

Family structure and substance use in 6,178 American Indian youth: a cross-sectional study.

OBJECTIVE: Adolescents from single-parent families are at significantly higher risk of substance use compared to those from mother-father families. More than half of American Indian (AI) children live in single-parent families, the second highest percentage among all groups. Given the paucity of research pertaining to the role of family structure and substance use in the AI population, we sought to examine this relationship. MATERIALS AND METHODS: Data from this study were obtained from the Substance Use Among American Indian Youth: Epidemiology and Etiology, [US], 2015-2020 study. Response variables of interest included age at first substance use, number of substances used, ever-use of substance, and substance use type (i.e., alcohol, cigarette, marijuana, etc.). RESULTS: Living in a father-only or mother-only setting showed a similar pattern of drug use. There was a significant increase in the risk of cigarette, alcohol and marijuana use. For cigarettes, the odds ratio was (OR = 2.60, 95% CI 1.80-3.75) in father-only setting compared to (OR = 1.42, 95% CI 1.13-1.78) for mother only setting. Alcohol use showed (OR = 1.72, 95% CI 1.19-2.50 and OR = 1.40, 95% CI 1.12-1.74) for father-only and mother-only respectively and marijuana use showed (OR = 1.59, 95% CI 1.10-2.30 and OR = 1.54, 95% CI -1.24-1.92) for father-only and mother-only respectively. CONCLUSIONS: Disturbed family structure is associated with increased risk of substance use among AI youth. This indicates the importance and need for policy and community level interventions to reduce youth substance exposure.

Assessment of natural and artificial radioactivity levels and radiation hazards and their relation to heavy metals in the industrial area of Port Said city, Egypt.

A detailed gamma ray spectrometry survey was carried out to make an action in environmental impact assessment of urbanization and industrialization on Port Said city, Egypt. The concentrations of the measured radioelements U-238, Th-232 in ppm, and K-40 %, in addition to the total counts of three selected randomly dumping sites (A, B, and C) were mapped. The concentration maps represent a base line for the radioactivity in the study area in order to detect any future radioactive contamination. These concentrations are ranging between 0.2 and 21 ppm for U-238 and 0.01 to 13.4 ppm for Th-232 as well as 0.15 to 3.8 % for K-40, whereas the total count values range from 8.7 to 123.6 uR. Moreover, the dose rate was mapped using the same spectrometer and survey parameters in order to assess the radiological effect of these radioelements. The dose rate values range from 0.12 to 1.61 mSv/year. Eighteen soil samples were collected from the sites with high radioelement concentrations and dose rates to determine the activity concentrations of Ra-226, Th-232, and K-40 using HPGe spectrometer. The activity concentrations of Ra-226, Th-232, and K-40 in the measured samples range from 18.03 to 398.66 Bq kg(-1), 5.28 to 75.7 Bq kg(-1), and 3,237.88 to 583.12 Bq kg(-1), respectively. In addition to analyze heavy metal for two high reading samples (a 1 and a 10) which give concentrations of Cd and Zn elements (a 1 40 ppm and a 10 42 ppm) and (a 1 0.90 ppm and a 10 0.97 ppm), respectively, that are in the range of phosphate fertilizer products that suggested a dumped man-made waste in site A. All indicate that the measured values for the soil samples in the two sites of three falls within the world ranges of soil in areas with normal levels of radioactivity, while site A shows a potential radiological risk for human beings, and it is important to carry out dose assessment program with a specifically detailed monitoring program periodically.

Metronomic capecitabine as extended adjuvant chemotherapy in women with triple negative breast cancer.

PURPOSE: High interest in triple-negative breast cancers is not surprising as this category of patients benefits neither from hormonal therapies nor from anti HER2 treatments. Blockade of angiogenesis by metronomic chemotherapy as well as other antiangiogenics might improve outcomes in this group of patients. This study aims to evaluate the tolerability and efficacy of metronomic capecitabine as extended adjuvant treatment for women with triple-negative breast cancer. METHODS: This is a prospective phase II study that included 41 patients diagnosed with triple-negative breast cancer and who were indicated for adjuvant chemotherapy. They received capecitabine 500mg PO twice daily and continuously for six months after finishing six cycles of adjuvant FEC100±postoperative radiotherapy. RESULTS: Forty-one patients were enrolled in this study between June 2010 and December 2013. Median age was 50years ranging from 27 to 67years. Treatment was well tolerated. Adverse effects were grade 1 palmar-plantar erythrodysesthesia in 13 patients (31.7%); grade 1 diarrhea in five patients (12.2%); and grade 1 vomiting in two patients (4.9%). Estimated median follow-up duration was 34 months. Estimated mean disease-free survival (DFS) was 42.4months (95% CI, 39.02-45.79), while median DFS was not reached. Estimated mean overall survival was 44.34months (95% CI 41.9-46.9). CONCLUSION: Extended adjuvant metronomic capecitabine is well tolerated with patient compliance. These results need to be compared in a study with control arm, larger sample, as well as longer follow-up.

CD14(+) HLA-DR low/(-) monocytes as indicator of disease aggressiveness in B-cell non-Hodgkin lymphoma.

INTRODUCTION: This study aimed to assess the correlation between the percentage of CD14(+) HLA-DR(low/-) immunosuppressive monocytes, plasma arginase 1 level, and disease aggressiveness in patients with B-cell non-Hodgkin lymphoma. METHODS: Forty-two patients with B-cell non-Hodgkin lymphoma and 20 healthy volunteers were enrolled in this study. Peripheral blood CD14+ HLA-DR(low/-) monocytes were detected by Flow cytometry, and their correlation with disease relapse and refractoriness was analyzed. RESULTS: The percent of CD14(+) HLA-DR(low/-) monocytes was significantly higher in the lymphoma patients than in the healthy controls (control, 9.3 ± 4%; lymphoma, 35.8 ± 20.2%; P < 0.0001), higher in stage III& IV than stage II (stage II, 26.48 ± 17%, n = 26; stage III & IV, 50.8 ± 15.4%, n = 16; P < 0.0001), more in diffuse large cell lymphoma than other pathology types and in relapsed/refractory patients than in patients who achieved remission during follow-up (relapsed/refractory, n = 18, 45.7 ± 16.7%; remission, n = 16, 21.4 ± 16.2%; P < 0.0001). The arginase I level correlated with increased percent of CD14(+) HLA-DR(low/-) monocytes (P < 0.0001). CONCLUSION: Increased CD14(+) monocytes with loss of HLA expression were seen in patients with higher stage disease, more aggressive pathology, and in relapse or refractoriness to treatment. Identifying therapeutic strategies to overcome the suppressive properties of these monocytes could be of value.

Stability-indicating spectrophotometric and spectrofluorimetric methods for determination of alfuzosin hydrochloride in the presence of its degradation products.

Validated stability-indicating spectrophotometric and spectrofluorimetric assays (SIAMs) were developed for the determination of alfuzosin hydrochloride (ALF) in the presence of its oxidative, acid, and alkaline degradation products. Three spectrophotometric methods were suggested for the determination of ALF in the presence of its oxidative degradation product; these included the use of zero order (0D), first order (1D), and third order (3D) spectra. The absorbance was measured at 330.8 nm for (0D) method, while the amplitude of first derivative (1D) method and that of third derivative (3D) method were measured at 354.0 and 241.2 nm, respectively. The linearity ranges were 1.0-40.0 microg/ml for (0D) and (1D) methods, and 1.0-10.0 microg/ml for (3D) method. Two spectrofluorimetric methods were developed, one for determination of ALF in the presence of its oxidative degradation product and the other for its determination in the presence of its acid or alkaline degradation products. The first method was based on measuring the native fluorescence of ALF in deionized water using lamda(excitation) 325.0 nm and lamda(emission) 390.0 nm. The linearity range was 50.0-750.0 ng/ml. This method was also used to determine ALF in human plasma with the aid of a suggested solid phase extraction method. The second method was used for determination of ALF via its acid degradation product. The method was based on the reaction of fluorescamine with the primary aliphatic amine group produced on the degradation product moiety. The reaction product was determined spectrofluorimetrically using lamda(excitation) 380.0 nm and lamda(emission) 465.0 nm. The linearity range was 100.0-900.0 ng/ml. All methods were validated according to the International Conference on Harmonization (ICH) guidelines, and applied to bulk powder and pharmaceutical formulations.

Colorectal cancer in a population with endemic Schistosoma mansoni: is this an at-risk population?

PURPOSE: Chronic infection with schistosomiasis has been clearly associated with the development of bladder cancer, and infestation is associated with a high incidence of colorectal cancer in endemic populations. Despite this association, the potential role of alterations in tumor suppressor genes colorectal cancers has never been evaluated in an endemically infected population. The aim of this paper was to compare histopathologic and genetic changes in schistosomal colitis-associated colorectal cancer (SCC) with colorectal cancer in a group of patients from the same population not affected by the disease (NDCC). MATERIALS AND METHODS: Sixty patients were included in this study: SCC-40, NDCC-20. Data collected included age, sex, clinical presentation, presence of synchronous tumors, histopathology, and clinical stage. p53, DCC (deleted in colorectal cancer gene), and mismatch repair genes (MLH1 and MSH2) were studied using immunohistochemical staining. RESULTS: Patients with SCC were significantly younger than the NDCC group (34.52+/-11.22 years vs 50.73+/-12.75 years, p=0.02). Mucinous adenocarcinoma occurred significantly more frequently in SCC (35 vs 10%, p=0.02). SCC tumors were more frequently stage III or IV, and significantly more synchronous tumors were present in the affected group (SCC-8/40 vs NDCC-1/20, p=0.05). p53 staining was far more frequent in SCC (SCC-32/40 vs NDCC-8/20, p=0.006). DCC expression was similar in two groups. There were only four cases, three in SCC and one in NDCC, that showed microsatellite instability. CONCLUSION: The data suggest that schistosomal colitis is more commonly associated with earlier onset of multicentric colorectal cancer, high percentage of mucinous adenocarcinoma, and presents at an advanced stage. The identification of a higher incidence of altered p53 expression in the SCC group raises the possibility of an association between schistosomiasis and alterations in p53 activation as an inciting event in colorectal cancer development.

Concentrations of salinomycin in eggs and tissues of laying chickens fed medicated feed for 14 days followed by withdrawal for 3 days.

Laying chickens were fed medicated feed containing various concentrations of sodium salinomycin (SAL) for 14 days followed by a 3 day withdrawal period. Eggs, collected during treatment and withdrawal, tissues and ovarian yolk of birds slaughtered after 0, 1, and 3 days' withdrawal were extracted and analysed by high performance liquid chromatography (HPLC). Tissues, ovarian yolk and freeze-dried egg albumen and yolk were extracted with acetone, followed by partitioning with petroleum ether and HPLC analysis. Albumen was extracted with methanol and analysed without further clean-up. Salinomycin was detected at 520 nm after post-column reaction with vanillin at 95 degrees C. Recoveries of fortified salinomycin from freeze-dried eggs (albumen and yolk) and tissue, premix and feed were nearly quantitative (> 90%), except liver which was < 85%. The detection limit was estimated to be 5 ng g-1, with the practical quantifiable limit being about 10 ng g-1. Highest SAL concentrations were in the more fatty components such as egg yolk, ovarian yolk and subcutaneous fat. SAL residues in other tissues were generally low and followed the order liver, kidney, thigh and breast muscles. SAL residues were dependent on the SAL concentration in feed and declined rapidly during withdrawal.

Clofazimin in the treatment of scleroma.

Scleroma is a chronic progressive granulomatous disease predominantly affecting the mucous membrane of the upper respiratory tract, endemic in temperate and tropical zone countries including Egypt. Many patients in early stages respond to medical treatment while others do not. In these patients an antileprotic agent Clofazimin (Lamprene) was tried in 76 patients and the therapeutic results are very promising, especially for the early stages of the disease.

Effects of white lupine in diets of growing turkeys.

In Experiment 1, dehulling white lupine (WL) improved growth and feed efficiency of male Large White turkey poults fed 40% WL during 4 to 21 days of age. In Experiment 2, WL was included proportionally with soybean meal in corn-soy diets of female turkeys from 0 to 17 wk of age. Soybean meal: WL ratios (S:WL) were 1:0 (control), 2:1, 1:1, and 6:1. At 17 wk of age hens on S:WL diets of 2:1 had body weights that were similar to those of birds fed the corn-soy control diets. Growth of hens fed S:WL diets of 6:1 was depressed (P less than .05). Growth depressions were greatest earlier in the study; older birds made compensatory gains. Feed efficiency of hens fed S:WL diets of 1:1 was poorer than that of controls during 0 to 11 wk but better than that of controls after 11 wk of age. Feed efficiency values were similar during 0 to 17 wk for hens fed control and S:WL diets of 2:1 and 1:1. Sensory evaluation of roasted light and dark meat of market birds revealed no taste differences in relation to WL level in the diet.

The molluscicidal properties of Ambrosia maritima L. (Compositae). 2. Results from a field trial using dry plant material.

A field trial in Egypt of the plant molluscicide, Ambrosia maritima is described. Applications of 140, 70 and 35 mg/l-1 dry, whole plant were made to irrigation canals and drains in June. The treatment effect took between 1 and 5 weeks to become fully established. The reduction in the numbers of alive Biomphalaria alexandrina snails was generally more than 90% and was virtually the same at all treatment levels and in both types of watercourse. The snail population remained at a low level for at least 3 months until September-October. The possible use of a single, annual application in April or May in controlling snails throughout the main schistosomiasis transmission season in Lower Egypt is suggested.

The molluscicidal properties of Ambrosia maritima L. (compositae). 1. Design for a molluscicide field trial.

The composite plant, Ambrosia maritima is toxic to the snail intermediate hosts of schistosomiasis. A field trial was required to confirm this activity. A preliminary survey of irrigation canals and drains was conducted using two snail sampling methods. The results have been used to indicate the minimum number of watercourses which would have to be treated and the number of sampling stations per watercourse required to establish statistical significance in a kill of snails obtained from a molluscicide treatment.

The effect of oestrogen on the nasal respiratory mucosa. An experimental histopathological and histochemical study.

An experimental histopathological and histochemical work carried out in thirty guinea-pigs of an average weight of 475 gm. receiving oestrogen in the form of ethynyl oestradiol in a dose of 10 microgram/animal/day and aiming at a study of the effects of oestrogen on the respiratory nasal mucosa. The histopathalogical lesions of the respiratory nasal mucosa were in the form of squamous metaplasia and spongiosis of the lining epithelium, with oedema of the underlying corium, glandular hyperplasia submucosal cellular infiltration, increased vascularity and some vascular changes in the form of endothelial proliferation with intimal thickening. Histochemical enzymatic alterations were in the form of increased succinic dehydrogenase activity in the epithelium as well as in the hyperplastic submucous glands, intensified reaction of the acid phosphatase in the cells of the corium, and the appearance of alkaline phosphatase activity in the apical parts of the cells lining the glands, indicating increased secretory activity. All the changes obtained in the histopathological and histochemical studies can be attributed to hormonal stimulation of the nasal mucosa.

PIP: The histopathological and histochemical effects of 10 mcg/day of eth inyl estradiol (EE) on the nasal respiratory mucosa were studied in 30 female guinea pigs. Histopathological changes observed after treatment were: 1) squamous metaplasia, 2) spongcosis and edema of the corium, 3) glandular hyperplasia, 4) cellular infiltrations, 5) increased vascularity, and 6) vascular changes in the form of endothelial proliferation with intimal thickening. The observed histochemical changes were: 1) increased succinic dehydrogenase activity in the epithelium and hyperplastic submucous glands, 2) an intensified reaction of acid phosphatase activity in the cells of the corium, and 3) alkaline phosphatase activity in the apical areas of the cells lining the glands. All of the observed changes are attributed to the stimulation of the nasal mucosa by EE.