Heparin, a highly sulfated and acidic glycosaminoglycan, has been clinically used in parenteral formulations to prevent and/or treat thromboembolic disorders for more than 90 years. Actions of heparin are not limited to anticoagulation and antithrombosis. Rather heparin has several other important actions which include fat clearing, antitumor and anti-inflammatory effects. However, use of heparin for such applications has been limited by its route of administration.<p> Historically, it has been believed that heparin is not absorbed following oral administration and therefore is only available for clinical use by parenteral administration. This belief has been challenged several times by our laboratory and other researchers showing heparin binding to endothelium following oral administration as well as prevention of thrombosis and lowering blood pressure, etc. However, the site of oral heparin absorption and the mechanism responsible for absorption have not been investigated. This in vitro study was designed to address these important questions.<p> We mounted pieces of rat gastrointestinal mucosa in a vertical diffusion Ussing chamber with both sides of the mucosal membrane exposed to Krebs bicarbonate buffer solution containing mannitol on the mucosal side (lumen) and glucose on the serosal side. Electrical properties across the membrane including potential difference (PD), resistance (R), and short circuit current (Isc) were recorded following heparin addition to the mucosal buffer under different mucosal buffer pH conditions. Mucosal and serosal buffer and tissue were collected and extracted for heparin and heparin recovery was performed by gel electrophoresis and anticoagulation tests. The first chapter (chapter 4) was designed to investigate if stomach mucosal tissue is a site for unfractionated heparin (UFH) absorption when mounted in the Ussing chamber. We found that stomach mucosa is able to transport UFH in an intact form when both mucosal and serosal buffers are at neutral pH of 7.4. When the mucosal buffer pH is made more acidic, at pH 4, transport is facilitated.<p> The second study (chapter 5) was designed to investigate if stomach mucosal tissue is also capable of transporting low molecular weight heparins (LMWHs). We showed that LMWHS were transported across stomach mucosa. However, the rate of transport was faster at mucosal buffer pH of 7.4 compared to pH 4.<p> The third study (chapter 6) investigated the effect of molecular weight on rate of heparin transport across stomach mucosal tissue since pH dependency of this transport was evident from both previous studies. This study suggested that decreasing the molecular weight increases the rate of heparin transport across stomach tissue under neutral pH but not acidic pH conditions. The fourth study (chapter 7) investigated how UFH is transported across the ileal mucosa and if Peyers patches contribute to this transport. It was shown that UFH is transported across ileal mucosa containing Peyers patches at a rate faster than ileal mucosa without Peyers patches. Making the mucosal buffer pH acidic facilitated UFH transport in the absence of Peyers patches but not when ileal mucosa contained Peyers patches.<p> The final study (chapter 8) investigated the mechanism of UFH transport across stomach mucosa mounted in the Ussing chamber using pharmacological inhibitors sodium fluoride, colchicine, and amiloride. Results showed that UFH is transported across the stomach mucosa at physiological acidic pH by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. From this, we conclude that oral heparins are absorbed across the gastrointestinal tract. The acidic environment of the stomach is a better absorption site for UFH. On the other hand, the more basic environment of the intestine is a better site for absorption of LMWHs. UFH is mainly absorbed across the stomach mucosa by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. Considering the very much larger surface area of the intestine than the stomach and that intestine, especially the ileum, contains many Peyers patches where UFH transport is not pH-dependent, larger amounts of UFH may be transported across the intestinal tissue compared to the stomach.

Heparin, a highly sulfated and acidic glycosaminoglycan, has been clinically used in parenteral formulations to prevent and/or treat thromboembolic disorders for more than 90 years. Actions of heparin are not limited to anticoagulation and antithrombosis. Rather heparin has several other important actions which include fat clearing, antitumor and anti-inflammatory effects. However, use of heparin for such applications has been limited by its route of administration.<p> Historically, it has been believed that heparin is not absorbed following oral administration and therefore is only available for clinical use by parenteral administration. This belief has been challenged several times by our laboratory and other researchers showing heparin binding to endothelium following oral administration as well as prevention of thrombosis and lowering blood pressure, etc. However, the site of oral heparin absorption and the mechanism responsible for absorption have not been investigated. This in vitro study was designed to address these important questions.<p> We mounted pieces of rat gastrointestinal mucosa in a vertical diffusion Ussing chamber with both sides of the mucosal membrane exposed to Krebs bicarbonate buffer solution containing mannitol on the mucosal side (lumen) and glucose on the serosal side. Electrical properties across the membrane including potential difference (PD), resistance (R), and short circuit current (Isc) were recorded following heparin addition to the mucosal buffer under different mucosal buffer pH conditions. Mucosal and serosal buffer and tissue were collected and extracted for heparin and heparin recovery was performed by gel electrophoresis and anticoagulation tests. The first chapter (chapter 4) was designed to investigate if stomach mucosal tissue is a site for unfractionated heparin (UFH) absorption when mounted in the Ussing chamber. We found that stomach mucosa is able to transport UFH in an intact form when both mucosal and serosal buffers are at neutral pH of 7.4. When the mucosal buffer pH is made more acidic, at pH 4, transport is facilitated.<p> The second study (chapter 5) was designed to investigate if stomach mucosal tissue is also capable of transporting low molecular weight heparins (LMWHs). We showed that LMWHS were transported across stomach mucosa. However, the rate of transport was faster at mucosal buffer pH of 7.4 compared to pH 4.<p> The third study (chapter 6) investigated the effect of molecular weight on rate of heparin transport across stomach mucosal tissue since pH dependency of this transport was evident from both previous studies. This study suggested that decreasing the molecular weight increases the rate of heparin transport across stomach tissue under neutral pH but not acidic pH conditions. The fourth study (chapter 7) investigated how UFH is transported across the ileal mucosa and if Peyers patches contribute to this transport. It was shown that UFH is transported across ileal mucosa containing Peyers patches at a rate faster than ileal mucosa without Peyers patches. Making the mucosal buffer pH acidic facilitated UFH transport in the absence of Peyers patches but not when ileal mucosa contained Peyers patches.<p> The final study (chapter 8) investigated the mechanism of UFH transport across stomach mucosa mounted in the Ussing chamber using pharmacological inhibitors sodium fluoride, colchicine, and amiloride. Results showed that UFH is transported across the stomach mucosa at physiological acidic pH by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. From this, we conclude that oral heparins are absorbed across the gastrointestinal tract. The acidic environment of the stomach is a better absorption site for UFH. On the other hand, the more basic environment of the intestine is a better site for absorption of LMWHs. UFH is mainly absorbed across the stomach mucosa by an active transport mechanism using metabolic energy, cytoplasmic tubule formation, and sodium-coupled systems. Considering the very much larger surface area of the intestine than the stomach and that intestine, especially the ileum, contains many Peyers patches where UFH transport is not pH-dependent, larger amounts of UFH may be transported across the intestinal tissue compared to the stomach.

No description available.

Se registraron 167 episodios de hemorragia digestiva alta (HDA) en el Instituto Especializado de Salud del Niño, de los cuales se incluyeron 136 episodios desde enero del 2000 a diciembre del 2004. Se realizó un estudio descriptivo retrospectivo. El objetivo general fue describir las características epidemiológicas, etiológicas, clínicas y de manejo de la Hemorragia Digestiva Alta. La prevalencia hospitalaria fue de 0.24 por 1000 atenciones/año. El mayor número de casos se presentó en varones (50.7%). El 94.1% se hospitalizó por emergencia, el servicios donde fueron hospitalizados con mayor frecuencia fue en gastroenterología (41.9%). El sangrado se inició en 96% fuera del hospital, los signos más frecuentes de presentación fueron la hematemesis y la melena. El 41.2% utilizó por lo menos un medicamento antes del sangrado, los antecedentes patológicos más frecuentes fueron los respiratorios y los gastrointestinales. El método de diagnóstico principal fue la endoscopía el cual se realizó en 61.3% de los casos. Las tres causas más frecuentes de diagnóstico fueron la gastritis en el 25.7%, seguido de las várices esofágicas en 18.4% y la úlcera duodenal 11.8%, no se estableció el diagnóstico en 13.2%. En 96.3% se usó tratamiento médico y solo en el 3.7% requirió manejo quirúrgico. En el 95.58% (130) se reportó mejoría del HDA y 6 pacientes fallecieron (4.42%). En conclusión se puede decir que la HDA es una enfermedad poco frecuente y se recomienda realizar un estudio prospectivo controlado para determinar mejor algunas variables epidemiológicas y clínicas, que ayudarían al mejor conocimiento de esta patología gastrointestinal.

Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 68-72).

Thesis (M.S.)--The University of North Carolina at Greensboro, 2008. / Title from PDF t.p. (viewed Mar. 19, 2010). Directed by Dennis LaJeunesse; submitted to the Dept. of Biology. Includes bibliographical references (p. 70-73).

Aims: To determine the contribution of Kirsten-ras and other abnormalities in the signalling pathway from growth factor to RAS in colorectal cancer and to develop a means of targeting a ras mutation of probable prognostic importance. Methods: Sections of 105 consecutive early colorectal cancers were obtained. DNA was extracted and codons 110-134 of the TGF- β RII receptor gene were amplified using PCR and screened for microsatellite instability. Codons 12 and 13 of the Kirsten-ras gene were identified by direct sequencing. Immunohistochemical staining was used to identify expression of pan RAS proteins, the growth factors EGF and TGF- β, and their common receptor, EGF-R. A ribozyme transcription unit was constructed to target the mRNA produced from Kirsten ras encoding a valine mutation at codon 12. The ribozyme was transcribed in colorectal cell lines using a novel expression/reporter plasmid. Two control ribozyme constructs were also used: one lacked ribozyme activity, the other was not transcribed in colorectal cells. Ribozyme expression and Kirsten-ras mRNA levels in transfected cells were identified by an RNase protection assay. Cell viability after transfection was determined by labelled thymidine uptake. Results: A ras pathway abnormality was identified in almost 90% of the tumours while microsatellite instability at the TGF- β RII gene was identified in only 3 (2.9%). Kirsten-Ras mutations were present in 30 (28.6%). Cleavage of target mRNA by the ribozyme in vitro and transcription in transfected cells were confirmed. However, there was no demonstrable reduction in Kirsten-ras mRNA in treated cells and no specific effect on cell viability.

Gastrointestinal tracts from 48 helmeted guineafowl (Numida meleagris), five Swainson’s spurfowl (Pternistis swainsonii) and a single Orange River francolin (Scleroptila levaillantoides) were examined for helminth parasites. Twelve species of helminths were found in helmeted guineafowl, comprising six nematodes, five cestodes and a single acanthocephalan.Six species of nematodes were recovered fromSwainson’s spurfowl and a single nematode was recovered from the Orange River francolin. First-year guineafowl had more than twice the intensity of infection than did adult guineafowl, particularly regarding the acanthocephalan Mediorhynchus gallinarum, the caecal nematodes Subulura dentigera and S. suctoria, and the cestodes Octopetalum numida, Hymenolepis cantaniana and Numidella numida. Female guineafowl had significantly higher intensities of infection than males, especially concerning M. gallinarum, S. dentigera and N. numida and the nematode Gongylonema congolense. The recovery of the cestode Retinometra sp. from helmeted guineafowl constitutes a new host-parasite record.

No description available.

No description available.