Physical activity and colon cancer

Heart disease and cancer, the major causes of mortality and morbidity in Western countries, have common risk factors. Exercise appears to reduce the risk of cardiovascular disease, but its role with respect to primary prevention of cancer has not been emphasized. Here we evaluate the epidemiological studies dealing with exercise and colon cancer. Despite the fact that different methods of assessing the amount of typical exercise of individuals and the different types of physical activity measured (occupational and recreational), there is remarkably consistent evidence that people who are highly physically active could be at a reduced risk of cancer of the colon. An analysis of case-control and cohort studies suggests that exercise might reduce the risk, at least in men, by up to one-third. We conclude that exercise has been overlooked as a potentially useful, effective, and acceptable method for reducing the risk of colon cancer.     

Visceral leishmaniasis in the BALB/c mouse: a comparison of the efficacy of a nonionic surfactant formulation of sodium stibogluconate with those of three proprietary formulations of amphotericin B

In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values, P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.     

Use of autologous fibrin glue in dermatologic surgery: application of skin graft and second intention healing

OBJECTIVE: To evaluate the efficiency of biological sealant, an autologous fibrin glue, in dermatological surgery. DESIGN: Randomized clinical trial. SETTING: The Dermatology Service of Hospital das Clinicas, Universidade de Campinas (UNICAMP), referral center. PATIENTS: 14 patients with malign epithelial cutaneous tumors participated in the evaluation, each having two tumors, generally facial and symmetrical, in order to perform a comparative evaluation on the same individual. PROCEDURES: The glue was prepared beforehand with a sample of autologous blood. Surgical extirpation of the tumor was followed by grafts or second intention healing. OUTCOMES: The efficiency of the sealant was then evaluated in relation to hemostasis, adhesion, surgical time and evolution of the granulation tissue, clinically and histologically. RESULTS: Immediate hemostasis and graft adhesion, with a significant reduction of surgical time, and in the open wounds there was immediate hemostasis and a clinical increase in granulation tissue, but with no histological differences among the groups on the 7th day. CONCLUSION: It is an adjuvant resource in skin cancer surgery.     

MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults

We have recently reported the isolation of a rat cDNA encoding a receptor-type tyrosine phosphatase, which appears to be a marker of thyroid differentiation. To elucidate the molecular mechanisms underlying r-PTPeta expression in normal thyroid cells both in vitro and in vivo, we investigated the regulation of r-PTPeta expression in cultured thyrocytes (the rat cell line PC Cl 3) and in an animal model of TSH-dependent thyroid goitrogenesis. In vitro studies showed that mRNA expression of r-PTPeta in thyroid cells is induced in a time- and dose-dependent manner by the activation of growth- and differentiation-linked PKA pathways (TSH and forskolin), whereas it is down-regulated by the activation of the proliferative dedifferentiating PKC-dependent transduction pathway (TPA). However, the regulation of r-PTPeta expression by TSH and TPA, respectively, is observed only in normal thyroid cells, but is lost in transformed thyroid cells. In vivo studies with thiouracil-fed rats demonstrated that increased serum levels of TSH up-regulated r-PTPeta mRNA expression in parallel with the stimulation of thyroid growth and function. The reduction of blood TSH levels due to iodide refeeding to goitrous rats determined a marked down-regulation of r-PTPeta expression, in parallel with involution of thyroid hyperplasia. Taken together these results demonstrate that the phosphatase r-PTPeta is regulated by the two main thyroid regulatory pathways and suggest that it may play an important role in the growth and differentiation of thyroid cells.     

Reproductive health in diabetic women. A report of two cases demonstrating the importance of preconception care

BACKGROUND: Optimal glycemic control prior to and during early pregnancy is essential in diabetic women. CASES: Two cases of fetal anencephaly occurred in diabetic women who conceived with medical technical assistance but did not receive preconception counseling. Both women had poor glycemic control periconceptually, as evidenced by elevated glycosylated hemoglobin determinations in the early first trimester. Targeted sonographic evaluations in the second trimester revealed both fetuses to be anencephalic. Both women terminated their pregnancies. CONCLUSION: Women with diabetes should be encouraged to seek preconceptual counseling and achieve tight glycemic control prior to attempting pregnancy. Health care providers play a vital role in stressing the importance of preconception care to these patients.     

Epitope tag mapping of the extracellular and cytoplasmic domains of the rat parathyroid hormone (PTH)/PTH-related peptide receptor

The PTH/PTH-related peptide (PTHrP) receptor is predicted to span the plasma membrane seven times with an amino-terminal extracellular extension and a cytoplasmic carboxyl-terminal tail. To assess this prediction, we inserted 10- or 9-amino acid epitope tags from c-myc or hemophilus influenza hemaglutinin (HA), which are recognized by the monoclonal antibodies 9E10 and 12Ca5, respectively, in different extracellular and cytoplasmic regions of the receptor and examined the immunoreactivity of the epitopes in intact and permeabilized cells. The data show that the epitopes were well tolerated when introduced into the E2 region of the extracellular amino-terminus (E2-myc and E2-HA), in the first extracellular loop (EL1), in the second and third cytoplasmic loops (CL2c and CL3), or in the carboxyl-terminal tail (T-myc). Receptors tagged at these locations were well expressed, bound PTH with high affinity, and increased cAMP accumulation with a good efficiency. Receptors tagged in the second and third extracellular loops (EL2c and EL3c) or the first cytoplasmic loop (CL1c) bound the PTH radioligand with a low affinity, stimulated cAMP accumulation with a low efficiency, and had low expression levels. The receptors tagged on presumed extracellular regions, E2-myc, E2-HA, EL1, EL2c, and EL3c, were readily detected on the surface of intact cells with the monoclonal antibody against the epitope tag. In contrast, receptors tagged with the c-myc epitope in the cytoplasmic loops (CL1c, CL2c, and CL3) or in the carboxyl-terminal tail (T-myc) did not show any 9E10 binding in intact cells. These receptors, however, were well expressed on the cell surface, as detected by the binding of the monoclonal antibody, 12Ca5, to the HA tag that was introduced into the E2 region of these constructs. The c-myc epitopes, however, became accessible after permeabilization of the cell membrane. In conclusion, these data provide experimental evidence for the sidedness of the extracellular and cytoplasmic domains of the PTH/PTHrP receptor.     

pH measurement: a comparison of results using glass membrane electrodes vs solid-state electrodes as a function of solution composition

We report a case of bilateral renal cell cancer and multiple lung metastasis who was first treated with left radical nephrectomy and nephron-sparing surgery of the right kidney. Consecutive interleukin-2 administration achieved partial response in lung disease and residual tumors were surgically removed. The disease-free state has continued for 33 months.     

Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13

Exposure of monocytes to pro-inflammatory cytokines or lipopolysaccharide (LPS) may induce synthesis and expression of tissue factor (TF). In this paper we have focused on the induction of TF-activity in human monocytes by the pro-inflammatory cytokines recombinant human interleukin 1 (rhIL-1 alpha) (rhIL-1 beta) (rhIL-6) and human tumour necrosis factor alpha (rhTNF-alpha), measured as procoagulant activity (PCA) in a microtitre plate-based clot assay. In addition we have studied the modulation of IL-1 alpha/beta induced TF-mRNA and PCA by rhIL-4, rhIL-10 and rhIL13. IL-1 alpha and IL-1 beta induced a concentration dependent increase in TF-activity. Neither IL-6 nor TNF-alpha gave rise to procoagulant activity at the concentrations tested (0.2-20 ng/ml). IL-4, IL-10 and IL-13, all effectively diminished IL-1 alpha/beta induced PCA, shown at the protein- and at the mRNA-level, while cell viability was unaffected. These results add to the previously demonstrated role of IL-4 and IL-10 as inhibitors of LPS-induced TF-activity, showing that these anti-inflammatory cytokines are not specific for LPS-activation but interfere with other stimulating substances such as IL-1, which may be involved in diseases where LPS is not present.