A comparison of risk factor investigation and experts' opinion elicitation analysis for identifying foot-and-mouth disease (FMD) high-risk areas within the FMD protection zone of South Africa (2007-2016).

Foot-and-mouth disease is a controlled disease in accordance with the South African Animal Diseases Act (Act 35 of 1984). The country was classified by the World Organisation for Animal Health (WOAH) as having a FMD free zone without vaccination in 1996. However, this status was suspended in 2019 due to a FMD outbreak outside the controlled zones. FMD control in South Africa includes animal movement restrictions placed on cloven-hoofed species and products, prophylactic vaccination of cattle, clinical surveillance of susceptible species, and disease control fencing to separate livestock from wildlife reservoirs. The objectives of this study were to evaluate differences in identifying high-risk areas for FMD using risk factor and expert opinion elicitation analysis. Differences in risk between FMD introduction and FMD spread within the FMD protection zone with vaccination (PZV) of South Africa (2007-2016) were also investigated. The study was conducted in the communal farming area of the FMD PZV, which is adjacent to wildlife reserves and characterised by individual faming units. Eleven risk factors that were considered important for FMD occurrence and spread were used to build a weighted linear combination (WLC) score based on risk factor data and expert opinion elicitation. A multivariable conditional logistic regression model was also used to calculate predicted probabilities of a FMD outbreak for all dip-tanks within the study area. Smoothed Bayesian kriged maps were generated for 11 individual risk factors, overall WLC scores for FMD occurrence and spread and for predicted probabilities of a FMD outbreak based on the conditional logistic regression model. Descriptively, vaccine matching was believed to have a great influence on both FMD occurrence and spread. Expert opinion suggested that FMD occurrence was influenced predominantly by proximity to game reserves and cattle density. Cattle populations and vaccination practices were considered most important for FMD spread. Highly effective cattle inspections were observed within areas that previously reported FMD outbreaks, indicating the importance of cattle inspection (surveillance) as a necessary element of FMD outbreak detection. The multivariable conditional logistic regression analysis, which was consistent with expert opinion elicitation; identified three factors including cattle population density (OR 3.87, 95% CI 1.47-10.21) and proximities to game reserve fences (OR 0.82, 95% CI 0.73-0.92) and rivers (OR 1.04, 95% CI 1.01-1.07) as significant factors for reported FMD outbreaks. Regaining and maintaining an FMD-free status without vaccination requires frequent monitoring of high-risk areas and designing targeted surveillance.

Efficacy of a foot-and-mouth disease vaccine against a heterologous SAT1 virus challenge in goats.

Goats are susceptible to infection with foot-and-mouth disease virus (FMDV), but their role in the epidemiology of the disease and response to vaccination is poorly understood. In southern Africa, FMDV serotypes Southern African Territories (SAT) 1, 2 and 3 are known to be endemic. In this study, we evaluated the efficacy of a pentavalent FMD vaccine in goats against heterologous challenge with a pool of field SAT1 FMDV. Forty FMD sero-negative goats (6-12 months of age) of mixed sexes were randomly allocated to one of five treatment groups: full cattle dose (2 ml), 1/3rd (0.67 ml), 1/6th (0.33 ml), 1/12th (0.16 ml) or unvaccinated placebo control. Goats were vaccinated with an inactivated pentavalent FMD vaccine containing serotypes SAT1, SAT2 and SAT3 on day 0 and revaccinated at day 20 post vaccination. Thereafter, thirty-four goats were challenged by tongue inoculation at day 41 post-vaccination using 104.57 50% tissue culture infective dose (TCID50) FMDV SAT1 pool. Animals were examined daily and clinical signs were scored. Rectal temperatures were measured daily, with temperatures ≥40 °C defined as fever. Clinical specimens (nasal, oral and rectal swabs) were collected on days 0, 2, 4 and 6 post challenge. Viral shedding was determined using reverse-transcriptase real-time PCR. None of the goats vaccinated with the full cattle dose developed secondary lesions. All vaccinated groups had lower temperatures compared to the unvaccinated controls (P < 0.001). Based on RT-PCR results, goats in the unvaccinated control group shed more virus compared to all groups except for 1/12th (P < 0.05), while goats in the full dose group shed less virus than goats in the 1/12th and the unvaccinated control group (P < 0.05). The results suggest that the 1/3rd (0.67 ml) dose of the vaccine is sufficient to reduce viral shedding after heterologous challenge with a FMDV SAT1 pool.

Serological responses of cattle inoculated with inactivated trivalent foot-and-mouth disease vaccine at the wildlife-livestock interface of the Kruger National Park, South Africa.

Foot-and-mouth disease (FMD) virus is economically one of the world's most important animal pathogens, which can be responsible for losses in livestock trade, as well as frequent and highly disruptive large-scale epidemics. The control of FMD in southern Africa typically includes vaccination of cattle with a trivalent or bivalent vaccine preparation. The objective of this study was to determine the level and duration of the antibody responses conferred by the current FMD vaccination programme in cattle at the western boundary of the Kruger National Park (KNP) in South Africa. Two hundred and eighty-three cattle from four communal dip tanks were longitudinally sampled after vaccination using an inactivated trivalent FMD vaccine (South African Territories (SAT) 1, SAT 2 and SAT 3). Blood samples were collected fortnightly over four months and antibodies were measured using a liquid-phase blocking ELISA. Only 5%, 43%, and 16% of enrolled cattle had evidence of pre-existing antibody responses to the three SAT viruses at the beginning of the study (≥1.6 log10 titre for SAT 1-3 respectively), which was 7-12 months after the last vaccination campaign. However, 14 days after vaccination this proportion increased to between 66% and 93%, with SAT 2 having the highest proportion. Young animals (<1 year old) tended to have higher predicted baseline antibody levels that peaked by 14 days. Positive serological responses were transient and by 56 days post-vaccination antibody levels begun to decline below the threshold of 1.6 log10 titre. Predicted peak antibody levels only consistently reached 2.0 log10 for SAT 2. Serological responses for SAT 2 tended to be longer, but in most cases the duration of antibody levels was short-lived. More research is necessary to determine the reasons for the limited duration of antibody responses, especially among younger cattle, in order to achieve more effective prophylactic vaccination.

Serological evidence of vaccination and perceptions concerning Foot-and-Mouth Disease control in cattle at the wildlife-livestock interface of the Kruger National Park, South Africa.

Communal livestock farming areas adjoining the Greater Kruger National Park Area within South Africa are part of the Foot-and-mouth disease (FMD) Protection Zone with Vaccination due to the proximity to wildlife reservoirs. FMD and its control affect the productivity of resource-poor farmers who often depend on livestock for their livelihoods. A cross-sectional study was performed with the objectives to evaluate the perceptions of farmers concerning FMD control, estimate the proportion of cattle with presumed protective antibody titres against FMD, as well as the proportion of herds with adequate herd immunity at the wildlife-livestock interface within Mpumalanga Province. One hundred and four farmers were interviewed with 73% (76/104) being cattle owners and the remainder hired cattle herders. The majority of respondents (79%, 82/104) reported a high level of satisfaction with the current animal health programmes in general. The educational level of the respondents varied by satisfaction level: the median (interquartile range; IQR) education level was standard 9 (2-12) for non-satisfied respondents, standard 3 (0-6) for little satisfied and standard 7 (2-11) for very satisfied respondents (P=0.036). Animals are not always treated at FMD inspections points, but satisfied respondents were more likely to seek veterinary assistance (P=0.001). The majority of respondents (92%, 96/104) identified the African buffalo (Syncerus caffer) as a risk factor for FMD outbreaks. Liquid-phase blocking ELISA antibody titres ≥1.6log10 were used to indicate positive serology secondary to FMD vaccination. At the time of sampling and relative to this threshold, 23% (95% confidence interval (CI): 12%-34%) of the sampled cattle had positive serology to SAT-1, 41% (95%CI: 33%-48%) to SAT-2 and 29% (95%CI: 19%-39%) to SAT-3. The median (IQR) time between the previous vaccination and sampling was 189 (168-241) days. The sampled cattle had a longer inter-vaccination interval as scheduled by state veterinary services and antibody levels were low at the time of the study. The majority of respondents expressed high satisfaction with the currently applied FMD vaccination programme, which provides an opportunity for progressive adaption of animal health programmes within the study area.

Characterization of Foot-and-Mouth Disease Viruses Collected in Nigeria Between 2007 and 2014: Evidence for Epidemiological Links Between West and East Africa.

This study describes the molecular characterization of 47 foot-and-mouth disease (FMD) viruses recovered from field outbreaks in Nigeria between 2007 and 2014. Antigen ELISA of viral isolates was used to identify FMD virus serotypes O, A and SAT 2. Phylogenetic analyses of VP1 nucleotide sequences provide evidence for the presence of multiple sublineages of serotype SAT 2, and O/EAST AFRICA 3 (EA-3) and O/WEST AFRICA topotypes in the country. In contrast, for serotype A, a single monophyletic cluster of viruses has persisted within Nigeria (2009-2013). These results demonstrate the close genetic relatedness of viruses in Nigeria to those from other African countries, including the first formal characterization of serotype O/EA-3 viruses in Nigeria. The introductions and persistence of certain viral lineages in Nigeria may reflect transmission patterns via nomadic pastoralism and animal trade. Continuous monitoring of field outbreaks is necessary to dissect the complexity of FMD epidemiology in sub-Saharan Africa.

Proteasome inhibitors: a novel class of potent and effective antitumor agents.

The ubiquitin-proteasome pathway plays a critical role in the regulated degradation of proteins involved in cell cycle control and tumor growth. Dysregulating the degradation of such proteins should have profound effects on tumor growth and cause cells to undergo apoptosis. To test this hypothesis, we developed a novel series of proteasome inhibitors, exemplified by PS-341, which we describe here. As determined by the National Cancer Institute in vitro screen, PS-341 has substantial cytotoxicity against a broad range of human tumor cells, including prostate cancer cell lines. The PC-3 prostate cell line was, therefore, chosen to further examine the antitumor activity of PS-341. In vitro, PS-341 elicits proteasome inhibition, leading to an increase in the intracellular levels of specific proteins, including the cyclin-dependent kinase inhibitor, p21. Moreover, exposure of such cells to PS-341 caused them to accumulate in the G2-M phase of the cell cycle and subsequently undergo apoptosis, as indicated by nuclear condensation and poly(ADP-ribose) polymerase cleavage. Following weekly i.v. treatment of PS-341 to mice bearing the PC-3 tumor, a significant decrease (60%) in tumor burden was observed in vivo. Direct injection of PS-341 into the tumor also caused a substantial (70%) decrease in tumor volume with 40% of the drug-treated mice having no detectable tumors at the end of the study. Studies also revealed that i.v. administration of PS-341 resulted in a rapid and widespread distribution of PS-341, with highest levels identified in the liver and gastrointestinal tract and lowest levels in the skin and muscle. Modest levels were found in the prostate, whereas there was no apparent penetration of the central nervous system. An assay to follow the biological activity of the PS-341 was established and used to determine temporal drug activity as well as its ability to penetrate tissues. As such, PS-341 was shown to penetrate PC-3 tumors and inhibit intracellular proteasome activity 1.0 h after i.v. dosing. These data illustrate that PS-341 not only reaches its biological target but has a direct effect on its biochemical target, the proteasome. Importantly, the data show that inhibition of this target site by PS-341 results in reduced tumor growth in murine tumor models. Together, the results highlight that the proteasome is a novel biochemical target and that inhibitors such as PS-341 represent a unique class of antitumor agents. PS-341 is currently under clinical evaluation for advanced cancers.

The lack of an effect by insulin or insulin-like growth factor-1 in attenuating colon-2-mediated cancer cachexia.

In several studies, the anabolic hormones insulin-like growth factor-1 (IGF-1) and insulin attenuated several metabolic changes associated with cancer cachexia. In the present study, we evaluated the effect of these hormones on the cachexia associated with colon-26 (C-26) tumor. Healthy age-matched and tumor-bearing mice were treated with two daily doses of IGF-1 (50 micrograms/kg in toto), or insulin (1 U in toto). Determinants of cachexia were body and tumor weight, epididymal fat pad and serum glucose concentrations. Neither IGF-1 nor insulin treatment had a significant effect on the cachectic parameters of C-26-bearing mice. These hormones were biologically active, being capable of inducing weight gain in hypophysectomized mice and hypoglycemia, respectively. Although IGF-1 and insulin have been used to treat cancer-related weight loss, the research presented here suggests that the beneficial effect of these hormones is not universal.

Influence of hypercortisolemia on the acute-phase protein response to endotoxin in humans.

BACKGROUND: The response to systemic infection includes the coordinated appearance of hepatic acute-phase proteins, the production of which may be influenced by a counterregulatory hormonal background. This study sought to assess the potential for hypercortisolemic conditions to influence fibrinogen kinetics and other acute-phase protein responses in humans with endotoxemia. METHODS: Eleven hospitalized healthy male volunteers underwent two separate determinations of fibrinogen kinetics, one baseline and one after administration of endotoxin (2 ng/kg intravenously; lot EC-5). Seven volunteers were studied without hormonal manipulation and four in the presence of a hypercortisolemic background (hydrocortisone infusion, 3 micrograms/kg/min). Fibrinogen fractional synthetic rates were estimated from the incorporation of orally administered 15N-glycine, and fibrinogen, C-reactive protein, cortisol, tumor necrosis factor-alpha, and interleukin-6 levels were also determined. RESULTS: The presence of an antecedent hypercortisolemic background resulted in an attenuated interleukin-6 response, as well as decreased fibrinogen synthesis and C-reactive protein appearance. CONCLUSIONS: The current data suggest that glucocorticoid hormonal influences are of importance in the regulation of endotoxin-induced cytokine and acute-phase protein responses.

The metabolic effects of pokeweed mitogen in mice.

Lectins are a family of proteins that stimulate cellular responses after binding to carbohydrate chains on plasma membranes. In the study described here, a mixture of lectins--pokeweed mitogen (PKW)--was shown to have insulinomimetic effects in mice. After receiving PKW (15 mg/kg intraperitoneally [IP]), serum glucose declined from 154 +/- 3 to 23 +/- 10 mg/dL by 24 hours later. Anorexia developed, and by 3 days, there was a significant decline in body weight. Carcass weights were 10% lower, and epididymal fat pad weights were 45% lower. When given for 16 days, PKW 3 mg/kg every other day caused a sustained 10% weight loss. Severe combined immune deficiency (SCID) mice were sensitive to PKW, showing that B and T lymphocytes were not required for the effects to develop. Cytokine antagonists attenuated the hypoglycemia and anorexia, but only by 50%. Further study showed that PKW has insulin-like effects in vitro. Glucose uptake was stimulated when murine C2C12 myotubes were exposed to an enriched fraction of PKW. These results demonstrated that PKW has both insulin-like activity and weight-reducing effects when administered to mice. The development of therapy for adult-onset diabetes or obesity based on lectins from pokeweed may be possible.

Are children with clefts underweight for age at the time of primary surgery?

Children with clefts, especially those with a cleft palate, have an impaired sucking mechanism and are therefore prone to nutritional problems. This study was undertaken to determine whether children with clefts of the lip and/or palate are underweight for age at the time of primary surgery. Underweight for age was defined as being less than 80 percent of expected weight for age or below the 3rd percentile as plotted on standard percentile charts. The records of all children with clefts seen at the Red Cross Children's Hospital between 1976 and 1996 were reviewed. Of these 740 records, 100 were excluded for inadequate data (47), severe systemic syndrome (27), no operation done (22), or craniofacial cleft (4). The records of 640 children were thus included; 195 (30.5 percent) were underweight for age. By comparison, only 13.7 percent of a similar group of noncleft controls (n = 872) were underweight for age. The difference between these two groups was highly significant (p < 0.01). Factors that influenced weight at the time of primary surgery were type of cleft and age at the time of surgery. Children with cleft palate, whether associated with a cleft lip or not, were found to be more underweight for age than those with an isolated unilateral cleft lip (p = 0.008). Children who had surgery after the age of 1 year were 1.5 times more likely to be underweight for age than children who had surgery under 1 year of age (p < 0.01). Children with isolated cleft palates who were underweight for age had a tendency toward a higher fistula rate (36 percent) than those of normal weight (24 percent) (p = 0.18).

Acute effects of hypophysectomy and administration of pancreatic and thyroid hormones on circulating concentrations of somatomedin-C in young chickens: relationship between growth hormone and somatomedin-C.

The short-term control of plasma concentrations of somatomedin C (SmC) in young chicks was examined by either surgical removal of the pituitary gland or by the administration of hormones which affect plasma concentrations of growth hormone (GH). As expected, removal of the source of GH by hypophysectomy reduced plasma concentration of GH, these being suppressed by 95.7% within 1 hour. Hypophysectomy was rapidly followed by reductions in the plasma concentration of SmC. For instance, plasma concentrations of SmC were decreased to 53% of pretreatment one hour following hypophysectomy. This suggests both that SmC has a short half life and that the release of SmC into the circulation is tightly coupled to the presence of pituitary hormone(s), presumably including GH. Sham surgery also decreased plasma concentrations of GH but were without effect on plasma concentrations of SmC. The short term control of plasma concentrations of SmC was also examined by the acute administration of hormones, which affect GH secretion in vivo. Injections of thyroxine or triiodothyronine decreased the plasma concentration of GH but were without effect on the plasma concentration of SmC. On the other hand, the administration of either glucagon or insulin decreased the plasma concentration of both GH and SmC. The present data suggest that plasma concentrations of SmC do not simply reflect the GH status in young chickens.

Cost implications of African swine fever in smallholder farrow-to-finish units: economic benefits of disease prevention through biosecurity.

African swine fever remains the greatest limitation to the development of the pig industry in Africa, and parts of Asia and Europe. It is especially important in West and Central African countries where the disease has become endemic. Biosecurity is the implementation of a set of measures that reduce the risk of infection through segregation, cleaning and disinfection. Using a 122-sow piggery unit, a financial model and costing were used to estimate the economic benefits of effective biosecurity against African swine fever. The outcomes suggest that pig production is a profitable venture that can generate a profit of approximately US$109,637.40 per annum and that an outbreak of African swine fever (ASF) has the potential to cause losses of up to US$910,836.70 in a single year. The implementation of biosecurity and its effective monitoring can prevent losses owing to ASF and is calculated to give a benefit-cost ratio of 29. A full implementation of biosecurity will result in a 9.70% reduction in total annual profit, but is justified in view of the substantial costs incurred in the event of an ASF outbreak. Biosecurity implementation is robust and capable of withstanding changes in input costs including moderate feed price increases, higher management costs and marginal reductions in total outputs. It is concluded that biosecurity is a key to successful pig production in an endemic situation.

Risk factors for farm-level African swine fever infection in major pig-producing areas in Nigeria, 1997-2011.

African swine fever (ASF) is an economically devastating disease for the pig industry, especially in Africa. Identifying what supports infection on pig farms in this region remains the key component in developing a risk-based approach to understanding the epidemiology of ASF and controlling the disease. Nigeria was used for this matched case-control study, because there is perpetual infection in some areas, while contiguous areas are intermittently infected. Risk factors and biosecurity practices in pig farms were evaluated in association with ASF infection. Subsets of farms located in high-density pig population areas and high-risk areas for ASF infection were randomly selected for analysis. Most plausible risk factor variables from the univariable analysis included in the multivariable analysis include: owner of farm had regular contact with infected farms and other farmers, untested pigs were routinely purchased into the farm in the course of outbreaks, there was an infected neighbourhood, other livestock were kept alongside pigs, there was a presence of an abattoir/slaughter slab in pig communities, wild birds had free access to pig pens, tools and implements were routinely shared by pig farmers, there was free access to feed stores by rats, and feed was purchased from a commercial source. Only the presence of an abattoir in a pig farming community (OR=8.20; CI(95%)=2.73, 24.63; P<0.001) and the presence of an infected pig farm in the neighbourhood (OR=3.26; CI(95%)=1.20, 8.83; P=0.02) were significant. There was a marginally significant negative association (protective) between risk of ASF infection and sharing farm tools and equipment (OR=0.35; CI(95%)=0.12, 1.01; P=0.05). Of the 28 biosecurity measures evaluated, food and water control (OR=0.14; CI(95%)=0.04, 0.46; P<0.001), separation/isolation of sick pigs (OR=0.14; CI(95%)=0.04, 0.53; P=0.004) and washing and disinfection of farm equipment and tools (OR=0.27; CI(95%)=0.10, 0.78; P=0.02) were negatively associated (protective) with ASF infection. Consultation and visits by veterinarian/paraveterinarians when animals were sick (OR=8.11; CI(95%)=2.13, 30.90; P=0.002), and pest and rodent control were positively associated with ASF infection of Nigerian farms (OR=4.94; CI(95%)=1.84, 13.29; P=0.002). The presentation of sick and unthrifty pigs for slaughter at abattoirs, farmers' inadvertent role, an infected neighbourhood, a pig to pig contact, rodents and wild birds may contribute to infections of farms, whereas washing, disinfection of tools, food and water control, and separation of sick pigs reduces the likelihood of infections. Underlying reasons for these observations and strategies for control are discussed.

Surveillance for African swine fever in Nigeria, 2006-2009.

African swine fever (ASF) has had significant economic and social impact in Nigeria since 1997. However, there has been no effective national response to bring it under control. In this report, we confirm that ASF is still prevalent and widespread in Nigeria. Results from both serosurveillance and virological analyses indicated that ASF is present in most of the agro-ecological zones of the country. Nine per cent (9%) of serum samples and 48% of tissue samples were positive for ASF virus antibody and genome, respectively. Areas with high pig-related activities (marketing, consumption and farming) have higher prevalences compared with areas with less pig activities. Farm-gate buyers, marketing systems and transport of untested pigs within the country assist with the circulation of the virus. Only by putting in place a comprehensive routine surveillance and testing system, reorganizing the market and transportation systems for pigs, implementing on-farm bio-security protocols and considering the option of compensation will it be possible to achieve a significant reduction in ASF prevalence in Nigeria.

An inhibitor of methionine aminopeptidase type-2, PPI-2458, ameliorates the pathophysiological disease processes of rheumatoid arthritis.

OBJECTIVE: To elucidate the role of methionine aminopeptidase type-2 (MetAP-2) in the clinical pathology of rheumatoid arthritis, arthritis was induced in rats by administration of peptidoglycan-polysaccharide (PG-PS). DESIGN: The inhibitor of MetAP-2, PPI-2458, was administered orally at 5 mg/kg every other day during 3 distinct phases of the disease. In vitro studies were performed to clarify in vivo findings. RESULTS: Ankle swelling was completely alleviated by MetAP-2 inhibition. Inhibition of MetAP-2 in blood and tissues correlated with protection against PG-PS-induced arthritis. Histopathology of the tarsal joints improved following PPI-2458 administration, including a significant improvement of bone structure. In in vitro studies, osteoclast formation and activity were inhibited by PPI-2458, a mechanism not previously attributed to MetAP-2 inhibition. CONCLUSIONS: The important role that MetAP-2 has in the pathophysiological disease processes of PG-PS arthritis provides a strong rationale for evaluating PPI-2458 as a disease modifying antirheumatic treatment for rheumatoid arthritis.

Insulin-like growth factor-1 activity is inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6.

With evidence that several proteins inhibit insulin-like growth factor (IGF) activity, we evaluated whether cytokines, which are elevated in many catabolic states, also affect IGF-1-mediated proteoglycan synthesis. Cartilage from hypophysectomized rats was exposed to the cytokines interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) in the presence or absence of IGF-1. IL-1 alpha inhibited IGF-1-stimulated proteoglycan (PG) synthesis > 95% at 20 ng/ml (p < 0.01). TNF-alpha and IL-6 caused a maximum inhibition of 56 and 54%, respectively, both at 200 ng/ml. Only in the absence of IGF-1 did IL-1 alpha inhibit PG synthesis below unstimulated levels, suggesting that although IL-1 alpha can directly inhibit PG synthesis, IL-1 alpha, TNF-alpha, TNF-alpha, and IL-6 each promotes cartilage loss also by inhibiting IGF-1-mediated anabolism.

Substrate cycling in lean and obese Zucker rats.

The objective of this study was to compare substrate cycling in lean and obese Zucker rats under conditions where there was (i) a nominal excess or (ii) a deficit in energy intake. Protein turnover was assessed by measuring protein synthesis and breakdown using 15N glycine as the tracer. Glucose/glucose-6-phosphate cycling was calculated from the difference in the glucose appearance rates measured using 2-D- and 6,6-D2-labeled glucose. Information on triglyceride/fatty acid cycling was obtained by measuring free fatty acid kinetics using 1-13C palmitate and glycerol kinetics using 5-D glycerol. Neither protein synthesis or breakdown or glucose cycling rates were significantly different between lean and obese Zucker rats. The relative rate of the triglyceride/fatty acid cycle was higher in the obese rat as a consequence of increased adiposity. Increased intake increased glucose cycling and decreased lipid cycling in both lean and obese rats. The findings indicate that substrate cycling is not different in obese rats and therefore is not a significant factor by which such animals maintain their severely obese state.

Vesnarinone inhibits immune-mediated but not Fas (CD95) agonist-mediated hepatic injury.

Previous studies have shown that the administration of concanavalin A (ConA) into mice induces immune-mediated liver injury, which can be largely abrogated by neutralizing tumor necrosis factor(TNF)alpha. Vesnarinone is an experimental drug which is known to inhibit TNF alpha release. Here we demonstrate that vesnarinone inhibits ConA-induced hepatic injury. In a dose-dependent manner, vesnarinone inhibits in several mouse strains the increase of serum aminotransferase concentrations. additional experiments show that vesnarinone inhibits ConA-mediated accumulation of DNA fragmentation in the liver. Furthermore, the drug significantly reduces the levels of circulating TNF alpha and interleukin-6 (IL-6). Vesnarinone does not modulate TNF alpha and IL-6 action on hepatic cells, as shown by its failure to reduce the cytokine specific-stimulation of acute phase plasma proteins in the rat hepatoma H-35 cell line. Neither vesnarinone nor anti-TNF alpha protect against direct liver injury induced by a sublethal dose of agonist anti-Fas (CD95) antibody. Taken together, these results suggest that vesnarinone blocks hepatic injury, in part by inhibiting the release of TNF alpha in vivo.

Repair of unilateral cleft lip: a comparison of five techniques.

Repair of unilateral cleft lip is a challenging procedure with no single technique satisfactory for all types of unilateral cleft deformity. This study compares retrospectively five techniques of unilateral cleft lip repair in 72 children (45 boys, 27 girls). Twenty-two children had a Millard rotation-advancement repair, 5 children had a Davies Z-plasty, 22 had a modified Z-plasty, 10 had a Tennison-Randall triangular flap repair, and 13 had a Nakajima-Yoshimura straight-line repair. Assessment was performed clinically by a plastic surgeon not involved in the original surgery. Repairs were assessed objectively by measurement of the vertical length of both the repaired and normal sides of the lip with calipers. Subjective criteria used to evaluate the repair were the symmetry of Cupid's bow, the quality of scar, the alignment of white roll, the evenness of the vermilion, and the lip pout. The mean follow-up period was 5.4 years (range, 9 months-29 years). Sixty-five of the 72 repairs measured (90%) were within two standard deviations (SDs) of normal and thus were considered to be of "acceptable" length. Seven repairs were unacceptably short (>2 SDs) on measurement, six of which included a rotation-advancement repair for a complete cleft lip. Subjective results paralleled the objective results. The outcome following repair of unilateral cleft lip was similar for all five surgical methods assessed except for complete cleft lips repaired by the rotation-advancement technique, which tended to result in an unacceptably short lip as measured on the repaired side.