Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Adjuvant immunosuppression for paradoxical deterioration in tuberculous meningitis including one case responsive to cyclosporine. A tertiary referral hospital experience.

BACKGROUND: Tuberculous meningitis (TBM) accounts for 1-4% of all tuberculosis (TB) presentations. Paradoxical deterioration in non-HIV patients is a common manifestation of anti-tuberculosis therapy, characterised by clinico-radiological deterioration. We report a case series of TBM admissions to our institution including one case with paradoxical deterioration refractory to corticosteroids who responded to adjuvant cyclosporine. METHODS: Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005-2016) with laboratory and/or radiologically confirmed TBM. RESULTS: Median patient age was 40 (range 22-81 years), M:F = 7:5. Eleven patients (92%) were of Asia-Pacific origin. Eleven initially presented with central nervous system manifestations and one had preceding miliary TB. Nine patients had extra-cranial TB involvement including eight with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. Paradoxical deterioration developed in three patients despite concomitant corticosteroids in two. One patient with paradoxical deterioration was refractory to corticosteroids: A 22-year-old Vietnamese male with TBM developed worsening headaches and altered mentation after seven weeks concomitant anti-TB and corticosteroid treatment. Interval MRI brain demonstrated increased size and number of tuberculomas as well as hydrocephalus. Cyclosporine was added with gradual improvement and ultimately good outcome. CONCLUSION: Our case series highlights the seriousness of paradoxical deterioration in TBM and the potential role of adjuvant cyclosporine in patients refractory to corticosteroids.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon ß/glatiramer acetate (IFNß/GA) to oral therapy are unknown. OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNß/GA, relative to a propensity-matched comparator of patients remaining on IFNß/GA. METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNß/GA ('stayers') using a Cox marginal model. RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26). CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

Treatment of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with intravenous immunoglobulin in a patient with multiple sclerosis treated with fingolimod after discontinuation of natalizumab.

We report a case of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome in a multiple sclerosis (MS) patient 3.5 months after fingolimod commencement and 4.5 months after natalizumab (NTZ) cessation. Three cerebrospinal fluid analyses were required before a definitive diagnosis of progressive multifocal leukoencephalopathy was reached. Intravenous immunoglobulin (IVIG) was subsequently given as the sole MS treatment along with mirtazapine and mefloquine. There has been improvement and subsequent clinical stabilization. The notable features are the difficult timing of fingolimod commencement in the context of previous NTZ therapy, the role of repeated cerebrospinal fluid John Cunningham virus analyses in progressive multifocal leukoencephalopathy diagnosis, and the role of IVIG.

Electrodermal hyporeactivity as a trait marker for suicidal propensity in uni- and bipolar depression.

BACKGROUND: A meta-analysis of studies investigating electrodermal activity in depressed patients, suggested that electrodermal hyporeactivity is sensitive and specific for suicide. AIMS: To confirm this finding and to study electrodermal hyporeactivity relative to type and severity of depression, trait anxiety, its stability and independence of depressive state. METHOD: Depressed inpatients (n = 783) were tested for habituation of electrodermal responses and clinically assessed using the Beck Depression Inventory (BDI) and the STAI-Trait scale for trait anxiety. RESULTS: The high sensitivity and raw specificity of electrodermal hyporeactivity for suicide were confirmed. Its prevalence was highest in bipolar disorders and was independent of severity of depression, trait anxiety, gender and age. Hyporeactivity was stable, while reactivity changed into hyporeactivity in a later depressive episode. CONCLUSIONS: The findings support the hypothesis that electrodermal hyporeactivity is a trait marker for suicidal propensity in depression.

Pasture dry matter consumption in European wild boars (Sus scrofa L.) as affected by herbage allowance.

The objective of this study was to evaluate the effect of herbage allowance on pasture DM consumption by growing European wild boar. An additional objective was to evaluate the influence of pasture consumption on supplemental diet intake and BW gain. A previously sown grass-clover pasture was managed by cutting to obtain an herbage mass equivalent to 1,500 kg/ha DM. Areas of pasture were limited by fencing to obtain 3 different herbage allowances whereas the pasture was removed in other areas. Forty-eight purebred European wild boars (initial age of 120 d and initial BW of 14.4 kg) were grouped in pairs and each pair was randomly allotted to 1 of 4 treatments (6 pairs per treatment): no pasture (4 m(2); pasture removed), low (5.33 m(2); 400 g/d pasture DM available/wild boar), medium (8 m(2); 600 g/d pasture DM available/wild boar), and high (16 m(2); 1,200 g/d pasture DM available/wild boar). The treatment areas were moved daily with a 7-d rotation. For a 28-d period, wild boars entered their treatment areas from 0830 to 1630 h, after which they had free access to a supplemental diet for 1 h. Pasture consumption was estimated daily by cutting pasture samples pre- and postgrazing. Supplemental diet consumption was determined daily (feed offered minus remaining feed). Animals were weighed weekly. Pasture consumption differed (P < 0.001) among wild boars receiving different treatments, with cumulative consumptions of 3.0 and 3.9 kg DM/wild boar over 28 d for low and medium herbage allowances, respectively (P < 0.09), and 6.4 kg DM/wild boar over 28 d for high herbage allowance, with the latter consumption being greater (P < 0.001) than the consumption recorded with the decreased herbage allowance treatments. The supplemental diet consumption tended (P = 0.16) to be less in wild boars with greater herbage allowance. European wild boars with access to pasture had greater (8.48 vs. 6.27 kg; P = 0.002) BW gain than those without access to pasture. In conclusion, pasture consumption by European wild boars can be enhanced by increasing herbage allowance and greater BW gains can be achieved in wild boars with access to pasture compared with those with no pasture access.

Improving infection prevention practice in primary and community care.

In March 2012, the National Institute for Health and Clinical Excellence (NICE) published an update of the 2003 guideline that addressed infection prevention and control of healthcare-associated infection in primary and community care settings. In the development of the guideline little high-quality evidence from randomized controlled trials was found. This is an area where high-quality research would impact on future updates of NICE guidance and more robust recommendations could then be made. This article summarizes the main research recommendations made in the guideline and describes the process of making research recommendations when evidence from systematic reviews is lacking.

Protective effects of transgenic human endothelial protein C receptor expression in murine models of transplantation.

Thrombosis and inflammation are major obstacles to successful pig-to-human solid organ xenotransplantation. A potential solution is genetic modification of the donor pig to overexpress molecules such as the endothelial protein C receptor (EPCR), which has anticoagulant, anti-inflammatory and cytoprotective signaling properties. Transgenic mice expressing human EPCR (hEPCR) were generated and characterized to test this approach. hEPCR was expressed widely and its compatibility with the mouse protein C pathway was evident from the anticoagulant phenotype of the transgenic mice, which exhibited a prolonged tail bleeding time and resistance to collagen-induced thrombosis. hEPCR mice were protected in a model of warm renal ischemia reperfusion injury compared to wild type (WT) littermates (mean serum creatinine 39.0 ± 2.3 µmol/L vs. 78.5 ± 10.0 µmol/L, p < 0.05; mean injury score 31 ± 7% vs. 56 ± 5%, p < 0.05). Heterotopic cardiac xenografts from hEPCR mice showed a small but significant prolongation of survival in C6-deficient PVG rat recipients compared to WT grafts (median graft survival 6 vs. 5 days, p < 0.05), with less hemorrhage and edema in rejected transgenic grafts. These data indicate that it is possible to overexpress EPCR at a sufficient level to provide protection against transplant-related thrombotic and inflammatory injury, without detrimental effects in the donor animal.

Low positive predictive value of the ABCD2 score in emergency department transient ischaemic attack diagnoses: the South Western Sydney transient ischaemic attack study.

BACKGROUND: The ABCD(2) stroke risk score is recommended in national guidelines for stratifying care in transient ischaemic attack (TIA) patients, based on its prediction of early stroke risk. We had become concerned about the score accuracy and its clinical value in modern TIA cohorts. METHODS: We identified emergency department-diagnosed TIA at two hospitals over 3 years (2004-2006). Cases were followed for stroke occurrence and ABCD(2) scores were determined from expert record review. Sensitivity, specificity and positive predictive values (PPV) of moderate-high ABCD(2) scores were determined. RESULTS: There were 827 indexed TIA diagnoses and record review was possible in 95.4%. Admitted patients had lower 30-day stroke risk (n = 0) than discharged patients (n = 7; 3.1%) (P < 0.0001). There was no significant difference in proportion of strokes between those with a low or moderate-high ABCD(2) score at 30 (1.2 vs 0.8%), 90 (2.0 vs 1.9%) and 365 days (2.4 vs 2.4%) respectively. At 30 days the sensitivity, specificity and PPV of a moderate-high score were 57% (95% confidence interval (CI) 25.0-84.2), 32.2% (95% CI 29.1-35.6) and 0.75% (95% CI 0.29-1.91) respectively. CONCLUSIONS: Early stroke risk was low after an emergency diagnosis of TIA and significantly lower in admitted patients. Moderate-high ABCD(2) scores did not predict early stroke risk. We suggest local validation of ABCD(2) before its clinical use and a review of its place in national guidelines.

Digestible energy content of pasture species in growing European wild boar (Sus scrofa L.).

The objectives were to determine the apparent energy digestibility of six pasture species frequently grazed by European wild boar (Sus scrofa L.) and to estimate the digestible energy (DE) consumption from pasture by grazing wild boar. Seven diets were prepared; a base diet (BD) which did not contain any pasture species, diets D1 to D5 which included 75% of the BD and 25% of the dried pasture species Lolium perenne (D1), Festuca arundinacea (D2), Agrostis capillaris (D3), Bromus staminius (D4) or Trifolium repens (D5) and D6 which contained 85% BD and 15% dried Plantago lanceolata. Seven purebred European wild boar (initial liveweight 24.4 ± 0.8 kg, average ± SEM) were given access to the diets following a Latin Square design. The animals received each diet for eight days, with faecal sampling on days 6, 7 and 8. The total apparent DE consumption from pasture by grazing wild boar was estimated using previously collected pasture consumption data from wild boar. The digestibility coefficients and DE contents of the pasture species ranged from 0.29 to 0.65, and 5.8 to 12.6 MJ/kg DM respectively, with L. perenne and P. lanceolata having the greatest digestibility coefficients and DE contents. The wild boar were estimated to satisfy between 52% and 142% of their maintenance energy requirements through pasture consumption. Grazing wild boar are able to utilise an important proportion of the energy present in pasture species.

Longitudinal assessment of anxiety, depression, and fatigue in people with multiple sclerosis.

OBJECTIVES: No longitudinal studies have concurrently evaluated predictors of anxiety, depression, and fatigue in people with multiple sclerosis (PwMS). This study determined factors that best predicted anxiety, depression, and fatigue in MS patients from a large pool of disease, cognitive, life-event stressor (LES), psychosocial, life-style, and demographic factors. DESIGN: A 2-year prospective longitudinal study evaluated predictors of psychological distress and fatigue in PwMS. METHODS: One hundred and one consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. LES, anxiety, depression, and fatigue were assessed at baseline and at 3-monthly intervals for 2-years. Disease, cognitive, demographic, psychosocial, and life-style factors were assessed at baseline. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: Depression strongly predicted anxiety and fatigue, and anxiety and fatigue strongly predicted later depression. Psychological distress (i.e. anxiety, depression) was also predicted by a combination of unhealthy behaviours (e.g. drug use, smoking, no exercise, or relaxation) and psychological factors (e.g. low optimism, avoidance coping), similar to the results of community-based studies. However, state-anxiety and fatigue were also predicted by immunotherapy status, and fatigue was also predicted by LES and demographics. CONCLUSIONS: These results suggest that similar factors might underpin psychological distress and fatigue in MS patients and community-well samples, although MS treatment factors may also be important. These results might assist clinicians in determining which MS patients are at greatest risk of developing anxiety, depression, or fatigue.

Evaluation of the chemical composition of dry dogfoods commercialized in Chile used for growing dogs / Avaliação da composição química de rações comerciais no Chile, usadas para filhotes

The nutritional quality of dry dogfood commercialized in Chile for growing dogs was studied. Samples from at least three different batches of 26 dogfood brands were mixed. The resultant samples (n=26) were chemically analyzed to determine their concentrations of dry matter (DM), gross energy, fiber, ash, crude protein, essential amino acids, total fat, linoleic acid and minerals. The metabolizable energy (ME) content of each sample was estimated using modified atwater factors. The results from the chemical analyses were compared with the nutrient profiles published by the American Association of Feed Control Officials (AAFCO). Dogfoods that were found to contain an estimated ME of over 4,000kcal/kg DM were corrected for their high energy density before comparison. All of the dogfoods contained adequate levels of protein, total fat, linoleic acid, iron, copper, manganese and selenium. The concentration of tryptophan was adequate in 92.3 percent of the samples. All of the other essential amino acids were present in adequate quantities. However, the situation was different for many of the minerals. Only 92.3 percent of the dogfoods contained an adequate Ca:P ratio. A total of 96.2 percent of the dogfoods contained an adequate level of Ca, 96.2 percent for P, 96.2 percent for Mg, 92.3 percent for I, 88.5 percent for Cl, 80.8 percent for Na, 80.8 percent for Zn and only 34.6 percent were adequate for K content. Overall, only 23 percent of the dogfoods evaluated in this study fulfilled all of the requirements established by the AAFCO in terms of their content of crude protein, amino acids, total fat, linoleic acid, and minerals. It appears that the majority of the dogfoods evaluated in this study (77 percent) would not satisfy all nutritional requirements of the growing dog.

Determinou-se a qualidade nutricional de 26 rações para filhotes caninos comercializadas no Chile. As rações foram analisadas quimicamente e comparadas com as recomendações da American Association of Food Control Officials (AAFCO). Para as análises, utilizou-se uma amostra de cada ração, composta de pelo menos três lotes diferentes. Para cada amostra, foram determinados os conteúdos de matéria seca (MS), fibra, proteína bruta, aminoácidos essenciais, gordura, ácido linoléico e minerais. A energia metabolizável foi determinada mediante os fatores de conversão de Atwater e corrigida por sua densidade quando ultrapassava 4000kcal/kgMS. Todas as rações apresentaram conteúdos adequados de proteína, gordura, ácido linoléico, ferro, cobre, manganês e selênio. A concentração de triptofano foi adequada em 92,3 por cento das rações, e a dos demais aminoácidos essenciais foi maior que a mínima recomendada. As maiores irregularidades foram encontradas no conteúdo de minerais, 92,3 por cento das rações apresentaram uma adequada relação Ca:P. Foram observados níveis adequados de Ca, P e Mg em 96,2 por cento das rações, de I em 92,3 por cento, de Cl em 88,5 por cento, de Na e Zn em 80,8 por cento e de K em 34,6 por cento. Em relação às concentrações de proteína, aminoácidos, gordura, ácido linoléico e minerais, somente 23 por cento das rações apresentavam todas as especificações recomendadas pela AAFCO. A maioria das rações analisadas, (77 por cento) apresentavam concentrações de nutrientes inferiores ao requerimento de filhotes caninos.

Relationship between stress and relapse in multiple sclerosis: Part I. Important features.

OBJECTIVE: The aim of this two-year prospective study was to examine the relationship between multiple aspects of life-event stress and relapse in multiple sclerosis (MS) patients. BACKGROUND: Few studies have defined the critical features of this life-event stress; for example, stressor duration, frequency, severity, disease-dependency, valency, or stressor constructs, such as the propensity to cause emotional distress/threat or the frustration of life goals. METHODS: 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life events were assessed at study-entry and at three-monthly intervals for two years. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: Acute events, but not chronic difficulties (CDs), predicted relapse occurrence: acute stressor frequency counts predicted greater relapse risk, along with low disability score (EDSS) and being male. We also confirmed the bi-directional stress-illness hypothesis: stressors predicted relapse, and relapse separately predicted stressors. CONCLUSIONS: Life-event stress impacts to a small degree on MS relapse. The number and not the severity of acute stressors are most important; chronic stressors do not predict later relapse. Males and those with early stage disease are also at greater risk of relapse. MS patients should be encouraged to reduce acute stressors during times of high stress, and feel reassured that disease-related chronic stressors do not increase their relapse risk.

Relationship between stress and relapse in multiple sclerosis: Part II. Direct and indirect relationships.

OBJECTIVE: The aim of this two-year prospective study was to determine which factors were: (i) directly related and/or (ii) indirectly related to multiple sclerosis (MS) relapse. These factors included life-event stressors, disease, demographic, psychosocial and lifestyle factors. BACKGROUND: Relatively little attention has been paid to the role of non-clinical relapse predictors (other than stressful life-events) in MS, or factors that indirectly impact on the stress-relapse relationship. METHODS: A total of 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life-events, depression, anxiety and fatigue were assessed at study-entry and at three-monthly intervals for two years. Disease, demographic, psychosocial and lifestyle factors were assessed at baseline. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: MS relapse was predicted by acute stressor frequency counts, coping responses that utilized social support, and being born in Australia, but not by chronic stressors, disease, demographic, psychosocial or lifestyle factors. No factors were found to indirectly impact on the stress relapse relationship. CONCLUSIONS: The number rather than severity of stressors was most important in relation to MS relapse risk, along with coping responses that utilized social support, suggesting that MS patients should avoid situations that are likely to generate multiple stressors or which provide few avenues for social support.

Nutritional evaluation of commercial dry dog foods by near infrared reflectance spectroscopy.

Near infrared reflectance spectroscopy (NIRS) was used to predict the nutritional value of dog foods sold in Chile. Fifty-nine dry foods for adult and growing dogs were collected, ground and scanned across the visible/NIR range and subsequently analysed for dry matter (DM), crude protein (CP), crude fibre (CF), total fat, linoleic acid, gross energy (GE), estimated metabolizable energy (ME) and several amino acids and minerals. Calibration equations were developed by modified partial least squares regression, and tested by cross-validation. Standard error of cross validation (SE(CV)) and coefficient of determination of cross validation (SE(CV)) were used to select best equations. Equations with good predicting accuracy were obtained for DM, CF, CP, GE and fat. Corresponding values for and SE(CV) were 0.96 and 1.7 g/kg, 0.91 and 3.1 g/kg, 0.99 and 5.0 g/kg, 0.93 and 0.26 MJ/kg, 0.89 and 12.4 g/kg. Several amino acids were also well predicted, such as arginine, leucine, isoleucine, phenylalanine-tyrosine (combined), threonine and valine, with values for and SE(CV) (g/kg) of 0.89 and 0.9, 0.94 and 1.3, 0.91 and 0.5, 0.95 and 0.9, 0.91 and 0.5, 0.93 and 0.5. Intermediate values, appropriate for ranking purposes, were obtained for ME, histidine, lysine and methionine-cysteine. Tryptophan, minerals or linoleic acid were not acceptably predicted, irrespective of the mathematical treatment applied. It is concluded that NIR can be successfully used to predict important nutritional characteristics of commercial dog foods.

Comparison of the enzyme-hydrolyzed casein, guanidination, and isotope dilution methods for determining ileal endogenous protein flow in the growing rat and pig.

The objectives of the two studies were to determine whether the guanidination and isotope dilution methods applied both by labeling the animal (15N-infusion method) and by diet (15N-dilution method) give similar estimates of ileal endogenous lysine (EL) and endogenous nitrogen (EN) flows, respectively, to that of the enzyme-hydrolyzed casein (EHC) method in the growing pig and to determine whether the guandination and 15N-dilution methods give similar estimates of EL and EN flows, respectively, to that of the EHC method in the rat. For the first study, the test diet contained guanidinated and enzymatically hydrolyzed casein (molecular weight < 5,000 Da), which was also labeled with 15N. Rats (n = 30; mean BW 178 g) and pigs (n = 6; mean BW 19.2 kg) received a preliminary EHC-based diet for 7 d. The test diet was then given to the rats and pigs on d 8. Digesta were sampled from the terminal 20 cm of ileum of killed animals. The EL flows determined using the guanidination method were lower than those determined using the EHC method (means of 298 vs. 382, and 214 vs. 287 microg/g of DMI, in the rat and pig, respectively; P < 0.05 for the rat and P < 0.01 for the pig). The EN flows determined with the 15N-dilution method were lower than those determined using the EHC method (means of 1,034 vs. 1,942 and 1,011 vs. 1,543 microg/g of DMI, in the rat and pig, respectively, P < 0.001 for the rat and P < 0.05 for the pig). In the second study, pigs (n = 6; mean BW 27 kg) were continuously infused via the jugular vein with 15N-leucine for 11 d. The pigs received an EHC-based diet (molecular weight < 5,000 Da) during this 11-d period, after which digesta were sampled at the terminal ileum under anesthesia. The EN flow determined using the 15N-infusion method (mean of 1,971 microg/g DMI) was higher (P < 0.01) than that determined using the EHC method (mean of 1,233 microg/g DMI). The guanidination method gave a lower estimate of EL flow than did the EHC method in both the pig and rat. The 15N-dilution method also gave a lower estimate of EN flow than the EHC method in the pig and rat, and the 15N-infusion method gave a higher estimate of EN flow than the EHC method in the pig.

Comparison of the endogenous ileal and faecal amino acid excretion in the dog (Canis familiaris) and the rat (Rattus rattus) determined under protein-free feeding and peptide alimentation.

The aim of the study was to determine and compare the endogenous ileal excretions of nitrogen and amino acids under protein-free and peptide alimentation by the dog and rat. Two diets were prepared, one that was devoid of protein and the other containing 23% enzyme hydrolysed casein. Chromic oxide was included in the diets as an indigestible marker. A total of 10 mixed breed dogs were fed hourly either a protein-free or enzymatically hydrolysed casein diet for a total of 10 days. A faecal sample was obtained from each dog on day 9 while digesta was obtained from the terminal 20 cm of the ileum directly after euthanasia on day 10. A total of 12 8-week-old Sprague-Dawley rats received the same diets as the dogs. A faecal sample from each rat was obtained on day 7 while ileal digesta samples were obtained on day 8. The endogenous ileal excretions of most amino acids were greater in the dogs and rats that received the enzymatically hydrolysed casein diet compared with those receiving the protein free diet. Whereas the pattern of endogenous amino acid excretion was similar in the rats and dogs, the dogs excreted a significantly greater amount of nitrogen (1.91 vs. 2.27 and 1.63 vs. 4.12 g/kg dry matter intake for the protein-free and peptide alimentation method, respectively) and all amino acids except for glycine, isoleucine and leucine. Endogenous ileal amino acid excretions are higher in dogs compared to omnivorous animals such as rats and pigs but similar to the carnivorous cat.

Il-4 therapy prevents the development of proteinuria in active Heymann nephritis by inhibition of Tc1 cells.

The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8(+) T-cytotoxic 1 (Tc1) cells and macrophages into glomeruli, as well as induction of Abs to Crry. Treatment with rIL-4 from the time of Fx1A/CFA immunization stimulated an earlier IgG1 response to Fx1A, induced anti-Crry Abs, and up-regulated IL-4 mRNA in lymphoid tissue, but did not alter proteinuria. Treatment with MRCOx-81, an IL-4-blocking mAb, resulted in greater proteinuria, which suggests endogenous IL-4 regulated the autoimmune response. Delay of rIL-4 treatment until 4 wk post-Fx1A/CFA immunization and just before the onset of proteinuria prevented the development of proteinuria and reduced Tc1 cell infiltrate in glomeruli. Delayed treatment with IL-4 had no effect on titer or isotype of Abs to Fx1A or on Ig, C3, and C9 accumulation in glomeruli. Treatment with rIL-13, a cytokine that alters macrophage function such as rIL-4, but has no direct effect on T or B cell function, reduced glomerular macrophage infiltrate, but did not prevent proteinuria or CD8+ T cell infiltrate. Anti-Crry Abs were paradoxically only induced with rIL-4 therapy, not in HN controls with proteinuria. It was concluded that the rIL-4 effect was probably by inhibition of Tc1 cells, which normally mediate the glomerular injury that results in proteinuria.