Gossypol Interferes with Both Type I and Type II Topoisomerase Activities Without Generating Strand Breaks

A considerable number of agents with chemotherapeutic potentials reported over the past years were shown to interfere with the reactions of DNA topoisomerases, the essential enzymes that regulate conformational changes in DNA topology. Gossypol, a naturally occurring bioactive phytochemical is a chemopreventive agent against various types of cancer cell growth with a reported activity on mammalian topoisomerase II. The compounds targeting topoisomerases vary in their mode of action; class I compounds act by stabilizing covalent topoisomerase-DNA complexes resulting in DNA strand breaks while class II compounds interfere with the catalytic function of topoisomerases without generating strand breaks. In this study, we report Gossypol as the interfering agent with type I topoisomerases as well. We also carried out an extensive set of assays to analyze the type of interference manifested by Gossypol on DNA topoisomerases. Our results strongly suggest that Gossypol is a potential class II inhibitor as it blocked DNA topoisomerase reactions with no consequently formed strand breaks. © 2012 Springer Science+Business Media New York

Saturated Fats: A Perspective from Lactation and Milk Composition

For recommendations of specific targets for the absolute amount of saturated fat intake, we need to know what dietary intake is most appropriate? Changing agricultural production and processing to lower the relative quantities of macronutrients requires years to accomplish. Changes can have unintended consequences on diets and the health of subsets of the population. Hence, what are the appropriate absolute amounts of saturated fat in our diets? Is the scientific evidence consistent with an optimal intake of zero? If not, is it also possible that a finite intake of saturated fats is beneficial to overall health, at least to a subset of the population? Conclusive evidence from prospective human trials is not available, hence other sources of information must be considered. One approach is to examine the evolution of lactation, and the composition of milks that developed through millennia of natural selective pressure and natural selection processes. Mammalian milks, including human milk, contain 50% of their total fatty acids as saturated fatty acids. The biochemical formation of a single double bond converting a saturated to a monounsaturated fatty acid is a pathway that exists in all eukaryotic organisms and is active within the mammary gland. In the face of selective pressure, mammary lipid synthesis in all mammals continues to release a significant content of saturated fatty acids into milk. Is it possible that evolution of the mammary gland reveals benefits to saturated fatty acids that current recommendations do not consider

Effects of rhG-CSF on neutrophil functions and survival in sepsis induced diabetic rats

Diabetic patients are more prone to infection and evidence for an immunologic defect superimposed upon the metabolic abnormalities of diabetes is convincing. Neutrophils play a critical role in the host defense mechanism against various bacterial infections, and it is suggested that impaired neutrophil functions cause susceptibility to infections in diabetic patients. To explore the possibility that Granulocyte colony-stimulating factor (G-CSF) may be useful to prevent the morbidity and mortality caused by infections in diabetics. We studied the effect of G-CSF against septicemia in diabetic rats

Prevalence and risk fators for gall bladder polyps

No Abstract. East African Medical Journal Vol. 84 (7) 2007 pp. 336-34

Effects of granulocyte-macrophage colony-stimulating factor on incisional wound healing in an experimental diabetic rat model

The exact nature of poor wound healing in diabetes is uncertain. Neutrophils play a critical role in the host defense mechanism, and it is suggested that impaired neutrophil functions cause healing difficulties with or without infections in diabetic patients. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically when given systematically to increase the circulating neutrophils, but its wound-healing effects have not been systematically studied. This study was undertaken to examine the effects of GM-CSF on incisional wound healing in an experimental diabetic rat model. Forty rats were randomly divided into three groups, group I receiving saline as control, diabetes-induced group II receiving saline and diabetes-induced group III receiving GM-CSF. The anesthetized rats in all groups were wounded 21 days after diabetes induction by streptozotocin. Blood neutrophil counts and neutrophil fractions were also determined three days after wounding. Tensile strengths of wounded skin and the hydroxyproline (hyp) level of the wound were determined and wound healing processes were evaluated by light and electron microscopy, fourteen days after wounding. Neutrophil counts and phagocytosis were significantly increased in group III and neutrophil counts decreased in group II (p < 0.05). Although the hydroxyproline level of wound tissue significantly decreased in group II as compared with group III (p < 0.05), there was no differences of tensile strength between group II and III (p < 0.05). Wound score in group II was less than that in groups I and III (p < 0.05). It is concluded that PMN may have a role in modulating wound healing. GM-CSF may be useful for creating better wound healing healing. GM-CSF may be useful for creating better wound healing in risky patients such as diabetics

The relationship between neutrophils and incisional wound healing

The systemic administration of granulocyte-macrophage colony-stimulating factor (GMCSF) is used clinically to increase circulating neutrophils, but its wound healing effects after intraperitoneal treatment have not been studied yet. We planned to investigate the effect of neutrophils on wound healing under cyclophosphamide and GM-CSF treatment. Forty rats were divided into three groups: control group (group I, n = 12) receiving saline, group II (n = 14) receiving cyclophosphamide and group III (n = 14) receiving GM-CSF. The rats in all groups underwent incisional wounding and were euthanized after 7 days. Blood neutrophil counts and functions, tensile strengths and the hydroxyproline level of skin were determined, and a histopathological evaluation of healing was made. Neutrophil counts and phagocytosis significantly increased in group III and decreased in group II. Although the skin hydroxyproline level did not differ, there was a difference in tensile strength of the wounded skin between group II and group III. The wound score in group II was lower than that in groups III and I. As a result we suggest that systemically given GM-CSF - by increasing the neutrophil count and neutrophil phagocytosis index - can enhance the tensile strength of surgical incisions. Copyright (C) 2001 S. Karger AG, Basel

The effect of granulocyte colony-stimulating factor on mortality rate in experimental sepsis [DENEYSEL SEPSISTE GRANULOSIT KOLONI-STIMULAN FAKTOR UYGULANMESININ MORTALITEYE ETKISI]

Neutrophils have an important role in the initial phase of host defense. One of the growth factors, Granulocyte Colony-Stimulating Factor (G-CSF) enhances neutrophil counts and functional capacity. The aim of this study was to investigate the effect of recombinant human (rh) G-CSF on mortality rate in an experimental sepsis model performed by 'Cecal Ligation and Puncture' (CLP) in rats. Totally 48 rats were separated into 3 groups and SF alone (Group I) or antibiotic alone (Group II) or antibiotic + G-CSF (Group III) were injected 24 hours before CLP procedure. The calculated absolute neutrophil counts of the blood samples taken by cardiac puncture at the 24th hour after CLP were significantly higher in Group III when compared to the other groups and the control samples which were taken before the study period (p0.05). Further investigations are necessary for G-CSF to be used widely in clinical pratice