Effect of a competitive inhibitor of platelet aggregation on experimentally induced laminitis in ponies

OBJECTIVES: To determining whether inhibition of platelet aggregation prevents development of carbohydrate overload-induced alimentary laminitis. ANIMALS: 22 healthy adult ponies. PROCEDURES: Acute laminitis was induced by oral administration of corn starch/wood flour to 16 ponies, 8 of which were treated with a synthetic analogue of the platelet fibrinogen receptor antagonist peptide (RPR) RGDS (arginine-glycine-aspartic acid-serine) 110885; 6 ponies served as negative controls. Blood was collected before and at 4, 8, 12, 24, 28, and 32 hours after administration of carbohydrate overload, and PCV, total plasma protein concentration, platelet count, activated clotting time, whole blood recalcification time, spontaneous platelet aggregation, ex vivo platelet aggregation responses, in vivo platelet activation, and platelet-neutrophil aggregates were evaluated. RESULTS: Of 16 ponies given carbohydrate, 6 of 8 untreated ponies developed laminitis and 0 of 8 ponies treated with RPR 110885 developed laminitis. The RPR 110885 treatment attenuated the increase in platelet-neutrophil aggregates observed in untreated ponies. CONCLUSIONS: Platelets are involved in the pathogenesis of equine alimentary laminitis. CLINICAL RELEVANCE: Platelet aggregation inhibitors may be useful for prevention or treatment of laminitis, or both.     

Structure of 5S rRNA within the Escherichia coli ribosome: iodine-induced cleavage patterns of phosphorothioate derivatives

The protection patterns of 5S rRNA in solution, within the ribosomal 50S subunit, 70S ribosomes, and functional complexes, were assessed with the phosphorothioate method. About 20% of the analyzed positions (G9-G107) showed strong assembly defects: A phosphorothioate at one of these positions significantly impaired the incorporation of 5S rRNA into 50S particles. The reverse has also been observed: A phosphorothioate is preferred over a phosphate residue in the assembly process at a few positions. The results further demonstrate that 5S rRNA undergoes conformational changes during the assembly in the central protuberance of the 50S subunit and upon association with the small ribosomal subunit forming a 70S ribosome. In striking contrast, when the 70S ribosomes are once formed, the contact pattern of the 5S rRNA is the same in various functional states such as initiation-like complexes and pre- and posttranslocational states.     

The antioxidant properties of lycopene

The antioxidant properties of the carotenoid lycopene were compared in three different model oxidative systems. In egg yolk liposomes, in the presence of 2.5 mM FeSO4 and 200 mM ascorbate, lycopene, alpha-tocopherol, and beta-carotene inhibited the accumulation of lipid peroxidation products reacting with 2-thiobarbituric acid (TBARS) in a dose-dependent mode, with the concentration of half-inhibition being 80, 30 and 130 mM, respectively. In the liposomes subjected to illumination with a He-Ne laser (632.8 nm) at a dose of 10.5 J/cm2, in the presence of 32.5 micrograms/ml hematoporphyrin derivatives (Fotogem, NIOPIC, Russia) TBARS accumulated, and this effect was inhibited by lycopene, alpha-tocopherol, and dihydroquercetin with approximately equal efficiencies (the half-inhibition concentrations were 10(-5) mM). In both systems studied, sodium azide at a concentration of 10 mM inhibited the TBARS accumulation by no more than 20%. Apparently, the inhibitory action of not only alpha-tocopherol, but also beta-carotene and lycopene was the result of their antiradical action, rather than quenching of the singlet oxygen in an aqueous medium. The introduction of lycopene, as well as beta-carotene in liposomes subjected to Fe(2+)-induced lipid peroxidation decreased the chemiluminescence (CL) intensity at the stage of CL slow flash, with no essential influence on the lag period. These data suggest that the effect of lycopene on lipid peroxidation was the result of its interaction with free radicals rather than chelating ferrous ions. The antiradical activity of lycopene was also confirmed by the method of luminol photochemiluminescence (PCL). Lycopene increased the PCL lag period (L) and decreased the PCL amplitude (A), which implies its antiradical and SOD-like activity in this system.     

Thymulin stimulates prolactin and thyrotropin release in an age-related manner

Reduction in the biomechanical competence of the axial skeleton can result in challenging complications. Osteoporosis consists of a heterogeneous group of syndromes in which bone mass per unit volume is reduced in otherwise normal bone, which results in more fragile bone. The geriatric population has an increased risk for debilitating postural changes because of several factors. The two most apparent factors are involutional loss of functional muscle motor units and the greater prevalence of osteoporosis in this population. Obviously, the main objective of rehabilitation is to prevent fractures rather than to treat the complications. These complications can vary from "silent" compression fractures of vertebral bodies, to sacral insufficiency fractures, to "breath-taking" fractures of the spine or femoral neck. The exponential loss of bone at the postmenopausal stage is not accompanied by an incremental loss of muscle strength. The loss of muscle strength follows a more gradual course and is not affected significantly by a sudden hormonal decline, as is the case with bone loss. This muscle loss may contribute to osteoporosis-related skeletal disfigurations. In men and women, the combination of aging and reduction of physical activity can affect musculoskeletal health, and contribute to the development of bone fragility. The parallel decline in muscle mass and bone mass with age is more than a coincidence, and inactivity may explain some of the bone loss previously associated with aging per se. Kyphotic postural change is the most physically disfiguring and psychologically damaging effect of osteoporosis and can contribute to an increment in vertebral fractures and the risk of falling. Axial skeletal fractures, such as fracture of the sacral alae (sacral insufficiency fracture) and pubic rami, may not be found until radiographic changes are detected. Management of chronic pain should include not only improvement of muscle strength and posture but also, at times, reduction of weight bearing on the painful pelvis with insufficiency fractures. Axial skeletal health can be assisted with improvement of muscular supportive strength. Disproportionate weakness in the back extensor musculature relative to body weight or flexor strength considerably increases the risk of compressing porous vertebrae. A proper exercise program, especially osteogenic exercises, can improve musculoskeletal health in osteoporotic patients. Exercise not only improves musculoskeletal health but also can reduce the chronic pain syndrome and decrease depression. Application of a proper back support can decrease kyphotic posturing and can expedite the patient's return to ambulatory activities. Measures that can increase safety during ambulatory activities can reduce risk of falls and fractures. Managing the musculoskeletal challenges of osteoporosis goes hand in hand with managing the psychological aspects of the disease.     

Natural honey prevents ischaemia-reperfusion-induced gastric mucosal lesions and increased vascular permeability in rats

OBJECTIVE: It has been proposed that natural honey may contain a 'sucralfate-like' substance. Recent studies have shown that sucralfate affords protection against ischaemia-reperfusion-induced injuries in the rat stomach. Therefore, the effect of honey was studied on ischaemia-reperfusion-induced gastric lesions, intraluminal bleeding, vascular permeability and non-protein sulphhydryls (NP-SH) in the rat stomach. METHODS: Rats were subjected to 30 min of gastric ischaemia in the presence of 100 mM HCl and reperfusion period of 60 min. Intraluminal bleeding was assessed macroscopically and the gastric lesions were graded microscopically under an inverted microscope. Vascular permeability was quantified by measuring spectrophotometrically the extravasated Evans blue dye in the stomach. NP-SH levels were measured spectrophotometrically. A luminol-dependent chemiluminescence method was used to assess antioxidant effects of honey in vitro. RESULTS: There were significantly more gastric lesions, more severe intraluminal bleeding, more leakage of Evans blue and depletion of NP-SH during the reperfusion period as compared to controls. Pre-treatment with honey (0.078-0.625 g/kg, orally) or dimethyl sulphoxide (0.02-0.08 g/kg, intraperitoneally) 30 min before the ischaemia-reperfusion dose-dependently reduced the gastric lesions and intraluminal bleeding and decreased the vascular permeability. Furthermore, honey reversed the ischaemia-reperfusion-induced depletion of NP-SH levels and inhibited the luminol-dependent chemiluminescence induced in a cell-free xanthine-xanthine oxidase system. CONCLUSION: These results suggest that gastric protection by honey may be a result of its antioxidant effect. It is suggested that this property of honey may be due to the presence of a 'sucralfate-like' substance.     

Evaluation of platelet activation and platelet-neutrophil aggregates in ponies with alimentary laminitis

OBJECTIVES: To determine whether platelets are hyperaggregable or form platelet-neutrophil aggregates during the prodromal stages of acute laminitis of ponies. ANIMALS: Healthy adult ponies: 8 experimental and 6 control. PROCEDURES: Acute laminitis was induced by oral administration of corn starch and wood flour to 8 ponies, and indices of platelet activation were evaluated. Blood samples were collected before and at 4, 8, 12, 24, 28, and 32 hours after carbohydrate administration, and PCV, total plasma protein concentration, platelet count, activated clotting time, whole blood recalcification time, spontaneous platelet aggregation, ex vivo platelet aggregation responses, and platelet-neutrophil aggregates were determined. When lameness was first detected, ponies were euthanatized and arteriography and histologic examination of hooves were performed. RESULTS: Carbohydrate overload was associated with hyperaggregability of platelets throughout the prodromal stages of laminitis and increased numbers of platelet-neutrophil aggregates. Reduction of blood supply to affected hooves was variable, and blood clots were found in 6 of 11 laminitis-affected hooves. CONCLUSIONS: Platelets were hyperaggregable throughout the prodromal stages of carbohydrate-induced laminitis and formed platelet-neutrophil aggregates. Platelet-neutrophil aggregates may initiate or contribute to development of acute laminitis. CLINICAL RELEVANCE: Anti-platelet therapy may be useful for treatment of acute alimentary laminitis in horses.     

Reduction in water permeability of the rabbit conjunctival epithelium by hypotonicity

The effects of unilateral exposure to hypotonic media on the diffusional water permeability of the isolated rabbit conjunctiva were determined. For these experiments, a segment of the bulbar-palpebral conjunctiva was mounted between Ussing-type hemichambers under short-circuited conditions. Unidirectional diffusional water fluxes (Jdw) were measured in either direction by adding 3H2O to one hemichamber and sampling from the other. Electrical parameters were measured simultaneously. Jdw were determined in control isosmotic conditions and after dilution of one of the bathing solutions from 290 to 108 mOsMolar. This hypotonic condition reduced Jdw by 25-30% (n = 17) when applied basolaterally and by 25% (n = 6) apically. The effects were reversible and were also obtained when the opposite bathing solution contained amphotericin B, selectively permeabilizing the contralateral cell surface. From concomitant changes in transepithelial electrical resistance as well as 14C-mannitol fluxes completed under identical conditions, arguments are presented that the above effect is best explained as a cell regulated reduction in membrane water permeability. Presumably both apical and basolateral membranes can down-regulate their water permeabilities. This response, suggesting a protective mechanism to help maintain cell volume from hypotonicity, was also seen in other studies using the amphibian bladder and the frog cornea, in which the effect was only obtained basolaterally. Thus, regulation of epithelial water permeability appears to be a basic trait common to both amphibians and mammals, although tissue differences exist.     

The role of cell communication in the pathogenesis of breast cancer]

OBJECTIVE: The aim of the study is to analyse long-term results of patients with small cell lung cancer (SCLC) treated at the same institution according to a prospective study including surgery, chemotherapy, and radiotherapy. METHODS: From 1981 to 1995, 104 patients with a proven histology of SCLC underwent surgery, chemotherapy, and radiotherapy. Fifty-one patients with operable stage I or II lesion received surgical resection followed by adjuvant chemotherapy and radiotherapy. Fifty-three patients with proved SCLC and clinical stage III received induction chemotherapy followed by surgery and radiotherapy. All patients received from four to six courses of chemotherapy and 36 had prophylactic cranial irradiation (PCI). All patients had follow-up for at least 1 year, and survival time was calculated from the date of the diagnosis until death or most recent follow-up. RESULTS: Ninety-six patients were male and eight female. We performed 29 pneumonectomies, eight bilobectomies, 66 lobectomies and one no resection. Regarding the clinical stage, 35 patients (33.6%) had stage I, 16 patients (15.4%) had stage II and 53 (51%) had stage III. Post-operative pathologic staging revealed stage I in 37 patients (35.6%), stage II in nine patients (8.6%), stage III in 45 patients (43.3%), and in 13 patients (12.5%) there was no more tumor. The 30-day mortality was 2% (two patients). Fourteen patients (13.4%) had post-operative complications. Fifty-one patients (49%) had a relapse. The median follow-up was 55 months. Twenty-six patients remain alive and 78 patients have died. The overall 5-year survival rate was 32%, with an estimate median survival time of 28 months; according to the pathologic stage, the survival data were 52.2%, 30% and 15.3% for stage I, II and III, respectively (P < 0.001). The 5-year survival was 41% in patients without SCLC after chemotherapy. CONCLUSION: As with non-small cell lung cancer, survival following surgery and chemotherapy clearly correlates with the stage. At present, it is not clear whether surgery is truly effective for patients with SCLC. In our experience, the complete elimination of small cell lung cancer is associated with an improvement in survival (41% at 5 years).