Assessment of Serum CoQ10 Levels and other Antioxidant Markers in Breast Cancer

Background: The balance of the oxidative state in the body is fundamental for the maintenance of homeostasis. It has been implicated in the onset and progression of several diseases including breast cancer. The way in which the Reactive Oxygen Species (ROS) / antioxidants balance leads to or responds to disease is still controversial. In this study, TAC is used as a reference for the total antioxidant power of the body and Coenzyme Q10 (CoQ10) for its vital importance in cellular antioxidant action and being the only lipid soluble antioxidant synthesized endogenously. Copper and zinc were measured as trace elements reflecting the antioxidant micronutrient profile of the body. Methods: After approval of the ethical committee, 60 recently diagnosed non-intervened breast cancer patients were recruited from the Medical Research Institute hospital, Alexandria University along with 20 apparently healthy volunteers as control group. Full patient history was taken including breastfeeding history, parity, hormone replacement therapy use, body mass index, pathological examination, metastatic work up results, past medical history and drug use. CA 15-3 and laboratory investigations evaluating blood glucose, kidney and liver functions were performed. Q10 levels were measured by HPLC using a kit from Recipe®. TAC was assayed spectrophotometrically (Biodiagnostics®). Copper and Zinc levels were determined by inductively coupled plasma-optical emission spectrometry. Results: There was a statistically significant increase in the CoQ10, TAC and copper levels in the breast cancer group when compared to the control group. Zinc showed no statistically significant difference between the studied groups. Conclusion: Inspite of the fact that a high antioxidant level is usually considered as a favourable state, TAC, CoQ10 and copper levels showed significantly higher levels in the breast cancer group when compared to the control group. It is worth mentioning that the cancer group were all recently diagnosed, non-intervened and showed no signs of metastasis. It is still unclear whether the increased antioxidant levels offer a selective growth advantage to tumor cells over their surrounding normal cells or serve as a protective measure by the body in an attempt to correct the assault triggered by the ROS.     

Hypertension in Jordanian children: a retrospective analysis of 70 cases

Seventy patients, aged 1–20 years, were seen at Jordan University Hospital with high blood pressure (BP) over a 3-year period. BP values ranged from 140 to 230 mmHg for systolic pressure and from 90 to 130 mmHg for diastolic pressure. Essential hypertension was seen in only 6 patients (8.6%); secondary hypertension (n=64 or 91.4%) was due to renal parenchymal diseases (RPD) in 46 patients (65.7%), reno-vascular lesions in 8 (11.4%), renal transplantation in 5 (7.2%), teenage pregnancy in 4 (5.7%), and phaeochromocytoma in 1 patient (1.4%). The aetiologies of RPD were as follows: end-stage renal disease requiring dialysis in 14 patients, acute glomerulonephritis in 14, idiopathic nephrotic syndrome in 10, chronic renal insufficiency in 5, and polycystic kidney in 3 patients. Surgical cure of hypertension was achieved in 5 of the children with reno-vascular lesions and in the patient with phaeochromocytoma.     

203Pb-labeled alpha-melanocyte-stimulating hormone peptide as an imaging probe for melanoma detection.

Peptide-targeted alpha-therapy with 7.4 MBq of (212)Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) ((212)Pb-DOTA-Re(Arg(11))CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to (212)Pb-DOTA-Re(Arg(11))CCMSH therapy. The purpose of this study was to evaluate the potential of (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH. METHODS: DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb in 0.5 M NH(4)OAc buffer at pH 5.4. The internalization and efflux of (203)Pb-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of (203)Pb-DOTA-Re(Arg(11))CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with (203)Pb-DOTA-Re(Arg(11))CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection. RESULTS: (203)Pb-DOTA-Re(Arg(11))CCMSH was easily prepared in NH(4)OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). (203)Pb-DOTA-Re(Arg(11))CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of (203)Pb-DOTA-Re(Arg(11))CCMSH activity internalized after a 20-min incubation at 25 degrees C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a biodistribution pattern similar to that of (212)Pb-DOTA-Re(Arg(11))CCMSH in B16/F1 melanoma-bearing mice. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor uptake of 12.00+/-3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43+/-1.12 %ID/g at 48 h after injection. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of (203)Pb-DOTA-Re(Arg(11))CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. (203)Pb showed 1.6-mm SPECT resolution, which was comparable to (99m)Tc. Melanoma lesions were visualized through SPECT/CT images of (203)Pb-DOTA-Re(Arg(11))CCMSH at 2 h after injection. CONCLUSION: (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH melanoma treatment.     

Metabolism of 3H- and 14C-labeled glutamate, proline, and alanine in normal and adrenalectomized rats using different sites of tracer administration and sampling

Alanine, glutamate and proline labeled with 14C and 3H were infused into fasted normal and adrenalectomized rats. Alanine was administered by the A-V mode (arterial administration-venous sampling), and glutamate and proline by both the A-V and V-A (venous administration-arterial sampling) modes. The kinetics of 14C alanine and 14C glutamate differed markedly from those of the tritium-labeled compounds, but there was little difference in the kinetics of 3H and 14C proline. The replacement rate calculated from the A-V mode for glutamate was about half that obtained in the V-A mode, but there was little difference with proline. The masses of the amino acids (total content of amino acids in the body) were calculated from the washout curves of the tritium-labeled compounds after the infusion of tracer was terminated. The masses for the normal rats were 407 mumol/kg for alanine, 578 mumol/kg for glutamate and 296 mumol/kg for proline. The so-called distribution spaces calculated conventionally from total masses and the amino acid concentrations in plasma are much greater than the volume of the body, reflecting the fact that amino acid concentrations in tissues greatly exceed those in plasma. Adrenalectomy markedly affected the kinetics of the three amino acids, and their replacement rates were greatly reduced. The proline and glutamate masses were reduced by at least one half, while that of alanine was unchanged. Adrenalectomy markedly reduced the conversion of proline to glutamate. The hydrocortisone regimen used in this study restored the metabolism of alanine and glutamate to normal, but had no effect on that of proline.     

Gentamicin administration via peritoneal dialysis fluid: the risk of ototoxicity.

In a prospective study on 47 patients, 16 mg of gentamicin per two litres dialysate was administered intraperitoneally at every cycle of intermittent peritoneal dialysis, carried out over the course of several days. Serum gentamicin sampling, pure tone audiometry and caloric tests were performed before and during the treatment. The gentamicin levels reached at the end of the thirtieth cycle were observed to be low. In view of this, the risk of acute ototoxicity was considered to be minimal. This was confirmed by the absence of clinical audiometric or vestibulometric evidence of toxicity.     

Myocardial injury during standard treatment of an adult with status asthmaticus.

Asthma affects 5%-10% of adults in the United States. Older adults (> 65 years) with asthma have higher rates of fatal asthma than younger adults. The occurrence of a respiratory emergency, such as status asthmaticus, would seem likely to create a situation of cardiopulmonary dysfunction conducive to myocardial ischemia. However, multiple studies of fatal or near-fatal asthma have failed to incriminate myocardial infarction as a contributing factor. We report a patient without underlying coronary artery disease who sustained myocardial injury consistent with myocardial ischemia and infarction during status asthmaticus while receiving recommended treatment without intravenous sympathomimetics or theophylline.     

Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species.

The activities of several flavonoids and the related nonflavonoid compound epicatechin were compared with respect to Cu(II)-induced strand scission of DNA by using two different assays. The same series of compounds was used to study the stoichiometry of Cu(II) reduction in the absence of DNA. The compounds were compared for their ability to generate superoxide, hydrogen peroxide and the Cu(II)-dependent production of hydroxyl radicals. Flavonoids were examined to assess the production of a charge-transfer complex with Cu and the rate of decay of the complexes were compared. All the compounds tested had some ability to cause DNA strand scission in the presence of Cu(II), with myricetin being the most active and galangin the least active. The ability to cause such scission correlated with the rate of decay of the charge-transfer complex, the ability to generate active oxygen species and with the stoichiometry of Cu(II) binding. Analysis of the data in the light of the structural differences between the flavonoids led to a discussion of alternative Cu(II)-sequestering mechanisms.     

Prompt elevations of PGE2 and thromboxane A2 metabolites in peripheral node efferent lymph of sheep following drainage area immunization

In the past decade, the main interest in the involvement of prostaglandin E2 (PGE2) in the immune response has been concerned with its role in immunomodulation (suppression) both in vitro and in vivo. Comparatively little attention has been devoted to its immunostimulatory role. It has been suggested that PGE2, like histamine, may function as a 'double agent', initially triggering, facilitating and augmenting a stimulatory immune response and later modulating, limiting and contributing to the turning off of this response. We here report an early (within minutes) immunostimulatory involvement of PGE2 (and thromboxane A2) in the sheep, with prompt elevations in levels of PGE2 and thromboxane B2 in popliteal lymph node efferent lymph following drainage area immunization with killed Salmonella muenchen bacteria. These elevations were associated with an increase in efferent lymph flow and an equally prompt but limited depression of lymphocyte outputs into efferent lymph ('shutdown', 'recruitment'). Local increases in blood flow and vascular permeability probably play important roles in these events.