THE EFFECT OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION AND PHARMACOTHERAPY ON SERUM PROTEIN S100B IN TREATMENT-RESISTANT DEPRESSION.

BACKGROUND: Transcranial magnetic stimulation (TMS) is considered an effective and fast option for treating patients with major depressive disorder. With the increase in treatment options, the determination of biomarkers that predict which treatment will benefit patients the most has been a matter of curiosity for researchers. SUBJECTS AND METHODS: In this study, we aimed to determine the changes in serum concentrations of S100B, a neurotrophic factor thought to play a role in psychiatric disorders after repetitive TMS (rTMS) and anti-depressant drugs (AD) therapy in patients with major depressive disorder(MDD).In this cohort study, rTMS was applied to the left dorsolateral prefrontal cortex(DLPFC) of drug-resistant MDD patients, while another group of MDD patients was treated with AD for three weeks. Patients were evaluated by psychometric tests and serum S100B concentration at baseline and following intervention. There was also a healthy control group in which patients' S100B values were compared at baseline. RESULTS: There is a population with a total of 48 participants.(16 healthy controls,16 anti-depressant treatment groups, 16 individuals who received rTMS in addition to anti-depressant ) A total of 48 participants completed the study, and the S100B levels of the rTMS group and the anti-depressant drug group were found to be significantly higher than the healthy control group. S100B values, which were higher in the anti-depressant and rTMS groups compared to healthy controls, showed a significant reduction in group time interaction (start and end of treatment). CONCLUSION: rTMS of DLPFC demonstrated an effective complementary treatment for treatment-resistant patients with MDD, especially for patients with relatively high serum S100B concentrations.

Post-weaning piglets fed with different levels of fungal mycotoxins and spray-dried porcine plasma have improved weight gain, feed intake and reduced diarrhea incidence.

Mycotoxins are responsible for economic losses in the swine production industry, especially during post-weaning, when piglets are physiologically immature. Spray-dried porcine plasma (SDPP), added to pig diets, may help reduce losses due to mycotoxins. This work investigates the effects of SDPP in post-weaning piglets fed with diets containing natural contaminants or with more contaminants (co-contamination by mycotoxins). Fifty-six castrated weaned piglets were used in a randomized 2 (0 and 6% of SDPP) x 2 (natural contamination or co-contamination with mycotoxin) factorial design, with seven experimental units of two piglets each. The natural contaminants were 0.95 µg/kg aflatoxins +450 µg/kg fumonisins. The co-contaminated diet contained 300 µg/kg aflatoxins +8000 µg/kg fumonisins. Animals were fed 15 days with experimental diets. Feed intake, weight gain, feed efficiency, diarrhea incidence, and economic feasibility of SDPP treatement were evaluated in three periods of five days each. There was no interaction (P < 0.05) between mycotoxins levels and SDPP. Feed intake, weight gain and feed efficiency were higher (P < 0.05) in diets supplemented with SDPP. Animals fed with SDPP showed lower (P < 0.05) diarrhea incidence in the 1-10 day and 1-15 day periods. The experimental dose of mycotoxins reduced (P < 0.05) weight gain at 11-15 days. SDPP proved to be economical feasible over the total experimental period (1-15 days). Spray-dried plasma improved weight gain, feed intake and reduced diarrhea incidence in piglets post-weaning, but did not correlate with various levels of mycotoxins.

Valores de referencia de la proteína S100beta en población pediátrica / Serum S100Beta protein reference values in a paediatric population

INTRODUCCIÓN: La proteína S100β se ha propuesto como posible biomarcador en patología neurológica, tanto crónica como aguda. Los valores normales de esta proteína están bien definidos en adultos, no así en niños, en los que los valores séricos parecen variar con la edad. Nuestro objetivo es describir valores de referencia de S100β sérica en niños de 0 a 14 años. MATERIAL Y MÉTODOS: Estudio prospectivo en 257 niños sanos. Se establecieron 3 grupos por edad (menores de 12 meses, de 12 a 24 meses y mayores de 24 meses). RESULTADOS: Se incluyó a 179 niños y 78 niñas. La edad media ± DE fue de 5,5 ± 3,75 años. La concentración sérica media de la proteína S100β en todo el grupo fue 0,156 (0,140-0,172) μg/l. En los menores de 12 meses, la concentración sérica de S100β fue de 0,350 (0,280-0,421) μg/l; 0,165 (0,139-0,190) μg/l en el grupo entre 12 y 24 meses y 0,121 (0,109-0,133) μg/l en el grupo de niños mayores de 24 meses. Se observó una relación inversa entre la edad y la concentración sérica de S100β, que desciende conforme se incrementa la edad. No se observaron diferencias en cuanto al sexo. CONCLUSIONES: La concentración de S100β permanece estable a partir de los 2 años de edad, siendo posible establecer unos valores de referencia de S100β para mayores de 2 años. En los 2 primeros años de vida, la concentración de S100β sérica es más elevada cuanto menor es la edad del niño. No se observan diferencias en el valor de S100β sérica entre ambos sexos

INTRODUCTION: S100β protein has been proposed as a potential biomarker for both chronic and acute neurological disorders. Reference values of this protein are well defined in adults but not in children, in whom serum levels appear to vary with age. Reference values for serum S100β in children from 0 to 14 years are presented. MATERIALS AND METHODS: A prospective study was conducted on 257 healthy children, who were divided into three age groups (under 12 months, 12 to 24 months and over 24 months). RESULTS: The study included179 boys and 78 girls, with a mean age of 5.5 (3.75) years. The mean serum concentration of protein S100β was 0.156 (0.140-0.172) μg/l. In children under 12 months, serum S100β concentration was 0.350 (0.280-0.421) μg/l; 0.165 (0.139-0.190) μg/l in the group between 12 and 24 months and 0.121 (0.109-0.133) μg/l in children older than 24 months. An inverse relationship was observed between age and serum S100β, which declines as age increases. No differences were observed between sexes. CONCLUSIONS: The concentration of S100β remains stable after two years of age, being possible to establish a baseline of S100β for over two years. During the first two years of life, S100β serum concentration is higher, the lower the age of the child. No differences in serum S100β levels between sexes are observed

Utilización de las proteínas séricas y caseínas como suplementos dietéticos para la prolongación del efecto de saciedad en mujeres obesas / Using whey proteins and caseins as dietetic supplements in regulation of satiating effect of overweight women

Se estudió el consumo de tres tipos de suplementos, proteínas del lactosuero, caseínas y maltodextrinas (control) en la disminución de la ingesta energética y prolongación del efecto de saciedad de 60 mujeres obesas. Después de 10 semanas, la reducción del peso corporal, IMC, % de grasa corporal y circunferencia de la cintura fue significativamente mayor (p < 0,001) en el grupo que consumió las proteínas lactoséricas frente a los otros dos grupos (control y caseínas). También se observa un descenso en la ingesta energética de -383 kcal/día en las mujeres que consumieron las proteínas de lactosuero frente a un descenso de -144 kcal/día en el grupo de caseínas y de tan solo -70 kcal/día en el grupo control. Finalmente la regulación del efecto de saciedad mediante escala visual analógica fue también más efectiva en el caso de las proteínas séricas, que en el caso de las caseínas y maltodextrinas (AU)

It has been studied the effect of three kinds of supplements (whey, casein and maltodextrin, as control) in the regulation of food intake and satiety of 60 overweight women. After 10 weeks, significant differences (p < 0.001) were found with regard to reduction of weight, IMC, % fat and waist circumference in the whey group against casein and control groups. A higher decrease of energy intake (-383 kcal/day) was also found in women who ate whey supplements, while in the casein and control group the decrease was only -144 and -70 kcal/day respectively. Finally, satiety effect was more efficiently promoted by whey against casein and maltodextrins (AU)

Comparative effectiveness of autologous blood-derived products, shock-wave therapy and corticosteroids for treatment of plantar fasciitis: a network meta-analysis.

OBJECTIVE: To compare the efficacy of autologous blood-derived products (ABPs), CSs and shock-wave (SW) therapy in the treatment of plantar fasciitis. METHODS: Electronic databases were searched for studies that compared ABPs, CSs and SW therapy for the treatment of plantar fasciitis, published up to June 2014. The primary and secondary outcomes were reduction in visual analogue scale (VAS) score at 3 and 6 months and odds ratio of treatment success, respectively. Groups were compared by traditional pair-wise meta-analysis and by network meta-analysis. RESULTS: Seven randomized controlled trials and three quasi-experimental studies that included 604 patients were enrolled. Pair-wise meta-analysis indicated a trend favouring ABPs over CSs regarding VAS reduction at 3 months; this benefit was significant in a subgroup analysis of platelet-rich plasma (PRP) vs CSs. There were no significant between-group differences in VAS reduction at 6 months and in treatment success. Network meta-analysis showed that ABPs had the highest probability of being the best treatment at 3 months, but ABPs were slightly inferior to SW for VAS reduction at 6 months. Although SW therapy had the highest likelihood of treatment success, the between-group differences in probabilities were less remarkable than those for pain reduction at 3 and 6 months. CONCLUSION: ABPs, followed by CSs, were best in providing relief from pain at 3 months. SW therapy and ABPs had similar probabilities of providing pain relief at 6 months, and were better than CSs at that time. Subgroup analysis indicated that an ABP regimen consisting of platelet-rich plasma improves treatment efficacy.

Whey and soy protein supplements changes body composition in patients with Crohn’s disease undergoing azathioprine and anti-TNF-alpha therapy / Suplementos de proteína de suero y soya cambia la composición corporal en los pacientes con enfermedad de Crohn sometidos con azatioprina y anti-TNF-alfa terapias

Background: Crohn’s disease (CD) is a chronic transmural inflammation of the gastrointestinal tract of unknown cause. Malnutrition associated with active CD has been reduced although obesity has increased. Dietary strategies such as those with high-protein have been proposed to reduce body fat. This study compares the effects of two supplements on the nutritional status of CD patients. Materials and Methods: 68 CD patients were randomized in two groups: whey protein group (WP) and soy protein group (SP). Using bioimpedance analysis, anthropometry and albumin and pre-albumin dosages the nutritional status was measured before starting the intervention and after 8 and 16 weeks. The disease activity was determined by Crohn’s Disease Activity Index and serum C-reactive protein dosage and dietary intake by 24h dietary recalls. Results: Forty-one patients concluded the study and both supplements changed body composition similarly. Triceps skin fold thickness (p< 0.001) and body fat percentage (p=0.001) decreased, whereas mid-arm muscle circumference (p=0.004), corrected arm muscle area (p=0.005) and body lean percentage (p=0.001) increased. Conclusions: For Crohn’s disease patients undergoing anti TNF-alpha and azatioprine therapies, supplementation with whey and soy proteins changes body composition through reduction of body fat and thus contributes to control inflammation (AU)

Introducción: La enfermedad de Crohn (EC) es un trastorno inflamatorio crónico transmural del tracto gastrointestinal de carácter desconocida. La desnutrición asociada con EC activa se ha reducido a pesar de la obesidad que ha aumentado. Se han propuesto estrategias dietéticas, como aquellos con alto contenido de proteínas para reducir la grasa corporal. Este estudio compara los efectos de dos suplementos sobre el estado nutricional de los pacientes con EC. Materiales y Métodos: Fueron randomizados en dos grupos 68 pacientes con EC: el grupo de proteína de suero y el grupo de proteína de soya. Se utilizó el análisis de bioimpedancia eléctrica, la antropometría y dosificaciones de albúmina y prealbúmina del estado nutricional midiéndose antes de comenzar la intervención y después de 8 y 16 semanas. La actividad de la enfermedad se determinó por Índice de Actividad de Enfermedad de Crohn (CDAI), dosificación en suero de la proteína C reactiva y la ingesta dietética por recordatorio de 24h. Resultados: Cuarenta y un pacientes concluyeron el estudio y ambos suplementos cambiaron la composición corporal de manera similar. El espesor del pliegue cutáneo del tríceps (p <0,001) y el porcentaje de grasa corporal (p = 0,001) se redujeron, mientras que la circunferencia muscular braquial (p = 0,004), el área muscular del brazo corregida (p = 0,005) y el porcentaje corporal magra (p = 0,001) han aumentado. Conclusiones: En los pacientes con enfermedad de Crohn sometidos con anti-TNF-alfa y terapias azatioprina, la suplementación con proteínas de suero de leche y de soya cambia la composición corporal a través de la reducción de la grasa corporal y por lo tanto contribuye para controlar la inflamación (AU)

Efficacy of dietary spray dried plasma protein to mitigate the negative effects on performance of pigs fed diets with corn naturally contaminated with multiple mycotoxins.

The ability of spray dried plasma protein (SDPP) to reduce the negative effects of multiple mycotoxins from naturally contaminated corn on weaned pig performance and health was investigated (n = 180; 6.84 ± 0.11 kg). For 12 d after weaning, pigs were fed phase 1 nursery diets with either 0% SDPP (PP0) or 6% SDPP (PP6). After 12 d, pigs were fed phase 2 diets for 3 wk. Pigs fed PP0 in phase 1 continued to be fed a phase 2 diet with no SDPP (PP0/PP0) or were fed a diet including corn naturally contaminated with multiple mycotoxins (M), labeled PP0/PP0M. Pigs fed SDPP in phase 1 were fed either a diet with no SDPP (PP6/PP0), a diet with M and no SDPP (PP6/PP0M), a diet with M and 3% SDPP (PP6/PP3M), or a diet with M and 6% SDPP (PP6/PP6M). During phase 1, pigs fed PP6 had increased (P < 0.05) ADG, ADFI, and G:F, whereas immunological parameters were not altered. During phase 2, pigs consuming PP0/PP0M had reduced ADG (P < 0.01) and ADFI (P < 0.05) in contrast to pigs fed PP0/PP0, whereas the performance of pigs fed PP6/PP0M was intermediate to pigs fed PP0/PP0M and PP6/PP0. The ADG and ADFI did not differ for pigs fed PP0/PP0M and PP6/PP0M during phase 2. Performance of pigs fed PP6/PP3M in contrast to pigs fed PP6/PP0M during phase 2 did not differ; however, these pigs had lower (P < 0.05) tumor necrosis factor α and tended (P = 0.094) to have lower DNA damage. During phase 2, ADG and ADFI of pigs fed PP6/PP6M did not differ from pigs fed PP6/PP0M, but G:F tended (P = 0.067) to be increased in pigs fed PP6/PP6M. Over the entire study period, pigs fed PP0/PP0M had reduced (P < 0.05) ADG and tended (P = 0.067) to have reduced ADFI. During this time, pigs fed PP6/PP0M tended to have greater ADG and ADFI (P = 0.093 and P = 0.067, respectively) compared with pigs fed PP0/PP0M. Overall, feeding a diet with SDPP improved growth performance and feed intake of young pigs directly after weaning. Feeding multiple M had a negative impact on growth performance of pigs during this trial. This response was more significant when pigs were not fed SDPP in phase 1. Overall, when combining phase 1 and 2 performance data, daily gain and feed intake tended to be reduced when pigs were not fed 6% SDPP in phase 1. This study indicates that the composition of diets fed immediately after weaning may be important for pigs that subsequently are under a M challenge.

Dietary plasma proteins attenuate the innate immunity response in a mouse model of acute lung injury.

We examined whether oral plasma protein supplements affect the innate immune response in a model of acute lung inflammation. Mice were fed diets supplemented with 8 % spray-dried plasma (SDP) or 2 % plasma Ig concentrate (IC) from day 19 (weaning) until day 34. The mice were challenged with intranasal lipopolysaccharide (LPS) at day 33 (and killed 24 h later for cytokine and leucocyte analyses) or at day 34 (and killed 6 h later for cytokine determinations). In bronchoalveolar lavage fluid (BALF), LPS increased the number of leucocytes by twenty-sevenfold, an effect that was partly prevented by both SDP and IC, and by twentyfold the percentage of activated monocytes, which was partly prevented by SDP. In the lung tissue, LPS increased the infiltrated leucocytes, and this effect was prevented in part by SDP. In unchallenged mice, both SDP and IC diets reduced the percentage of resident neutrophils and monocytes (P < 0·05). In the blood, both SDP and IC completely prevented LPS-dependent monocyte activation (CD14⁺; P < 0·05). LPS dramatically increased the concentration of cytokines (TNF-α, IL-1α, IL-6, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor) and chemokines (CXCL1, CCL2, CCL3 and CCL4) in BALF. The acute response of cytokine production was reduced by 20-80 % by both SDP and IC. For chemokines, plasma supplements had no effect on LPS-induced CXCL1 expression but significantly reduced CCL2, CCL3 and CCL4 production (P < 0·05). The results support the view that dietary plasma proteins can be used to attenuate endotoxin-associated lung inflammation.

[Proteins influencing the blood coagulation]. / Proteine mit Einfluss auf die Blutgerinnung.

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death.

Identification of safe, effective treatments to mitigate toxicity after extensive radiation exposure has proven challenging. Only a limited number of candidate approaches have emerged, and the U.S. Food and Drug Administration has yet to approve any agent for a mass-casualty radiation disaster. Because patients undergoing hematopoietic stem cell transplantation undergo radiation treatment that produces toxicities similar to radiation-disaster exposure, we studied patients early after such treatment to identify new approaches to this problem. Patients rapidly developed endotoxemia and reduced plasma bactericidal/permeability-increasing protein (BPI), a potent endotoxin-neutralizing protein, in association with neutropenia. We hypothesized that a treatment supplying similar endotoxin-neutralizing activity might replace the BPI deficit and mitigate radiation toxicity and tested this idea in mice. A single 7-Gy radiation dose, which killed 95% of the mice by 30 days, was followed 24 hours later by twice-daily, subcutaneous injections of the recombinant BPI fragment rBPI21 or vehicle alone for 14 or 30 days, with or without an oral fluoroquinolone antibiotic with broad-spectrum antibacterial activity, including that against endotoxin-bearing Gram-negative bacteria. Compared to either fluoroquinolone alone or vehicle plus fluoroquinolone, the combined rBPI21 plus fluoroquinolone treatment improved survival, accelerated hematopoietic recovery, and promoted expansion of stem and progenitor cells. The observed efficacy of rBPI21 plus fluoroquinolone initiated 24 hours after lethal irradiation, combined with their established favorable bioactivity and safety profiles in critically ill humans, suggests the potential clinical use of this radiation mitigation strategy and supports its further evaluation.

A rat model of mild intestinal inflammation induced by Staphylococcus aureus enterotoxin B.

The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration of Staphylococcus aureus enterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines.

Tirucallic acids are novel pleckstrin homology domain-dependent Akt inhibitors inducing apoptosis in prostate cancer cells.

Activation of the serine/threonine kinase Akt is associated with aggressive clinical behavior of prostate cancer. We found that the human prostate cancer cell lines LNCaP and PC-3 express predominantly Akt1 and Akt2. Selective down-regulation of Akt1, but not Akt2, by short-hairpin RNA reduced the viability of prostate cancer cells. In addition, structurally different Akt inhibitors were cytotoxic for the prostate cancer cells, confirming that the Akt pathway is indispensable for their viability. We have purified the tetracyclic triterpenoids 3-oxo-tirucallic acid, 3-alpha-acetoxy-tirucallic acid, and 3-beta-acetoxy-tirucallic acid from the oleogum resin of Boswellia carterii to chemical homogeneity. The acetoxy-derivatives in particular potently inhibited the activities of human recombinant Akt1 and Akt2 and of constitutively active Akt immunoprecipitated from PC-3 cells, whereas inhibitor of nuclear factor-kappaB kinases remained unaffected. Docking data indicated that these tetracyclic triterpenoids form hydrogen bonds within the phosphatidylinositol binding pocket of the Akt pleckstrin homology domain. Accordingly, 3-beta-acetoxy-tirucallic acid did not inhibit the activity of Akt1 lacking the pleckstrin homology domain. In the prostate cancer cell lines investigated, these compounds inhibited the phosphorylation of cellular Akt and the Akt signaling pathways, including glycogen synthase kinase-3beta and BAD phosphorylation, nuclear accumulation of p65, the androgen receptor, beta-catenin, and c-Myc. These events culminated in the induction of apoptosis in prostate cancer, but not in nontumorigenic cells. The tirucallic acid derivatives inhibited proliferation and induced apoptosis in tumors xenografted onto chick chorioallantoic membranes and decreased the growth of pre-established prostate tumors in nude mice without overt systemic toxicity. Thus, tirucallic acid derivatives represent a new class of Akt inhibitors with antitumor properties.

Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

Effect of animal plasma proteins on intestinal damage and recovery of neonatal pigs infected with rotavirus.

Rotaviruses infect and elicit diarrhea in neonates of most mammalian species and cause 800,000 infant deaths a year. We used neonatal piglets to study the effects of dietary animal plasma proteins on intestinal health following rotavirus infection. Plasma protein contains a diverse mixture of functional components with biological activity and improves the health of animals challenged with other diarrhea-causing pathogens. In a 2 x 2 factorial design, we compared plasma protein- and soy protein-based diets in rotavirus-infected and noninfected piglets to determine if plasma protein reduced acute rotavirus intestinal damage or improved recovery. All infected animals shed rotavirus particles in their feces. Infected, plasma protein-fed piglets maintained growth rates similar to noninfected piglets in the first 3 days of infection; however, soy protein-fed piglets experienced reduced gains. Furthermore, infected, plasma protein-fed piglets showed no clinical signs of diarrhea. Infection reduced intestinal villus height and the villus height/crypt depth ratio by Day 3 of infection; however, reductions were not attenuated with dietary plasma protein. Infected, plasma protein-fed pigs maintained greater intestinal mucosa protein and estimated total lactase activity than infected, soy protein-fed piglets. Plasma proteins contain growth factors that may aid in rate of recovery as well as virus-binding proteins that may reduce infection pressure in the intestine. These data, combined with findings from other studies using plasma proteins in animal models of diarrhea, indicate the potential for using plasma proteins to improve the health of diarrheic neonates.

Susceptibility to thrombin-induced platelet microbicidal protein is associated with increased fluconazole efficacy against experimental endocarditis due to Candida albicans.

Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study evaluated the relationship between in vitro tPMP-1 susceptibility (tPMP-1s) or resistance (tPMP-1r) and efficacy of fluconazole (FLU) therapy of IE due to C. albicans. Candida IE was established in rabbits with either tPMP-1s or tPMP-1r strains. Treatment groups received FLU (100 mg/kg/day) intraperitoneally for 7 or 14 days; control animals received no therapy. At these time points, cardiac vegetations, kidneys, and spleens were quantitatively cultured to assess fungal burden. At both 7 and 14 days and in all target tissues, the extent of candidal clearance by FLU was greater in animals infected with the tPMP-1s strain than in those infected with the tPMP-1r strain. These differences were statistically significant in the spleen and kidney. Corroborating these in vivo data, FLU (a candidastatic agent), in combination with tPMP-1, exerted an enhanced fungicidal effect in vitro against tPMP-1s and tPMP-1r C. albicans, with the extent of this effect greatest against the tPMP-1s strain. Collectively, these results support the concept that tPMP-1 susceptibility contributes to the net efficacy of FLU against C. albicans IE in vivo, particularly in tissues in which platelets and tPMP-1 likely play significant roles in host defense.

Effects of substance S-1 on rats with impaired hearing.

Intraperitoneal administration of substance S-1 to male Wistar rats with impaired hearing markedly increased hearing acuity. Substance S-1 had no negative effects on hearing in intact animals.

Influence of in vitro susceptibility phenotype against thrombin-induced platelet microbicidal protein on treatment and prophylaxis outcomes of experimental Staphylococcus aureus endocarditis.

Thrombin-induced platelet microbicidal protein-1 (tPMP-1) is a small, cationic staphylocidal peptide from rabbit platelets. In the current study, the outcomes of vancomycin treatment and prophylaxis were compared in experimental infective endocarditis (IE) caused by an isogenic Staphylococcus aureus strain pair differing in tPMP-1 susceptibility (tPMPS) or resistance (tPMPR) in vitro (ISP479C and ISP479R, respectively). Vancomycin therapy (selected for its intrinsically slow bactericidal activity) reduced ISP479C (but not ISP479R) densities in vegetations compared with controls (P<.01). In contrast, prophylactic administration of vancomycin yielded no differences in efficacies for the 2 challenge strains. These data suggest that the tPMPR phenotype in vitro has a negative effect on the antimicrobial therapy (but not the prophylaxis) of experimental S. aureus IE. These disparate results may be explained in part by the requirement for microbicidal effects in the treatment of established IE, whereas prophylactic efficacy depends more on growth inhibitory and antiadhesion effects.

Recombinant N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) prevents shock-induced microcirculatory alterations in the liver.

OBJECTIVE: To investigate the effects of the recombinant 21-kilodalton N-terminal fragment of recombinant bactericidal and permeability increasing protein (rBPI21) on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock. DESIGN: Prospective, randomized, blinded, and placebo-controlled experimental study. SETTING: University research laboratory. SUBJECTS: Anesthetized Sprague-Dawley rats, weighing 220 to 250 g. INTERVENTIONS: Rats were subjected to 60 mins of hemorrhagic shock and subsequent resuscitation to sufficiently restore systemic circulation. The microcirculation of the liver was investigated by intravital fluorescence microscopy 5 hrs after hemorrhagic shock. Four shock groups were compared with a sham-control group. Shock groups received either rBPI21 (10 mg/kg) or placebo either before or after shock period. MEASUREMENTS AND MAIN RESULTS: No differences were observed in hemodynamic, respiratory, or metabolic parameters between the shock groups. However, the hepatic microcirculation showed severe deterioration 5 hrs after shock, indicated by significantly narrowed sinusoids in all shock groups compared with controls (8.5 +/- 0.3 microm vs. 10.0 +/- 0.4 pm). Leukocyte adhesion was markedly increased to comparable values in both placebo groups (619 cells/mm2 and 644 cells/mm2; sham, 168 cells/mm2). Neutralization of endotoxin by administration of rBPI21 before or after shock resulted in plain reduction of pathologic leukocyte-endothelial interaction (138 cells/mm2 and 85 cells/mm2). CONCLUSION: The results support the hypothesis that endotoxin induces microcirculatory alterations after shock, and further suggest a potentially beneficial role of rBPI21 in the treatment of posttraumatic endotoxin-induced inflammatory reactions.

Modification of late radiation damage in the rectum of rats by deproteinized calf blood serum (ActoHorm) and pentoxifylline (PTX).

PURPOSE: Prevention and treatment of radiation-induced late rectal ulcer using deproteinized calf blood serum (ActoHorm) or pentoxifylline. MATERIALS AND METHODS: Rectal ulcers were induced in Wistar rats using single X-ray doses of 20, 22 and 24 Gy. ActoHorm or pentoxifylline were given at various times after irradiation. The induced rectal damage was assessed by clinical examination, rectoscopy and histology of the post-mortem specimens. RESULTS: Neither ActoHorm nor pentoxifylline affected the incidence or latency or had any pronounced effect on healing of late rectal ulcers. Histological examination showed increased regenerative activity of the mucosal epithelium in all ActoHorm treated animals. CONCLUSION: Neither ActoHorm nor pentoxifylline prevented the development of radiation-induced rectal ulcers. The stimulation of mucosal epithelium with ActoHorm might, however, be effective in healing of superficial erosions of the intestinal mucosa.