Persistent measles infection in malnourished children.

Thirty malnourished and 25 well-nourished children were studied six to 31 days after the onset of a measles rash. Evidence of the virus was found in 40% of the malnourished children but in none of the well-nourished controls. Giant cells were found in the nasal secretions of five out of 17 malnourished children and measles antigen was detected in the lymphocytes of eight out of 28. The malnourished children showed depressed cell-mediated immunity to measles and candida antigens and a low response to meningococcal vaccine. Fifteen died from intercurrent infections. Malnutrition was thought to have depressed the immune response in these children, resulting in a severe and prolonged attack of measles. This, in turn, led to further damage to the immune system and more severe malnutrition. Thus these children were made susceptible to intercurrent infection.     

Effect of Toluene and Nutritional Status on Serotonin,Lipid Peroxidation Levels and NA<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase in Adult Rat Brain

The aim was to evaluate the effect of toluene and nutritional status on levels of serotonin (5-HT), 5-hydroxytryptophan (5-HTP), Na⁺/K⁺-ATPase, total ATPase and lipid peroxidation (TBARS) in rat brain. Study was conducted with malnourished (MN), well-nourished (WN) and normal Wistar rats. Three groups were formed for each nutritional status: control group I received 0.9% NaCl; toluene (1 g/kg) was administered to group II, and 1.5 g/kg to group III. Levels of 5-HT decreased (P < 0.05) in WN toluene groups, and 5-HTP decreased (P < 0.05) in the WN 1 g toluene and MN 1.5 g toluene groups. TBARS decreased (P < 0.05) in WN toluene groups. A trend to increase in Na⁺/K⁺-ATPase was found in WN and MN toluene groups, while total ATPase increased (P < 0.05) in the WN 1.5 g toluene group. The results suggest that high concentrations of toluene in single doses induce significant changes in the serotonergic system and alter membrane fluidity more perceptibly in the brain of adult animals with regular diet than in malnourished animals.     

Evaluation of Biochemical,Hematological and Parasitological Parameters of Protein-Deficient Hamsters Infected with Ancylostoma ceylanicum

Background

Hookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model.

Methodology/Principal Findings

Hamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as “malnourished”) and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool.

Conclusions

In this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection.     

Differential gene expression in lymphocytes from malnourished children

Malnutrition, which is widespread in developing countries, may be particularly devastating during childhood, when tissue development is occurring and nutrient requirements are great. Since protein-energy malnutrition potentially involves many cellular alterations, we have evaluated gene expression changes in lymphocytes from malnourished children using differential hybridization cloning. A cDNA library was generated from well-nourished children and differential screenings were performed with cDNAs obtained from well-nourished and malnourished children who presented with bacterial gastrointestinal infections. Differential expression was detected for genes involved in cell development and differentiation, and for genes involved in lymphocyte and mitochondrial functions. The genes detected in the present study suggest mechanisms for the changes in cell growth and immune function that are associated with protein-energy malnutrition. Two down-regulated genes in malnourished children may represent mechanisms of protection against immunosuppression. This finding clearly merits further investigation.     

Malnutrition promotes prostaglandin over leukotriene production and dysregulates eicosanoid-cytokine crosstalk in activated resident macrophages

We previously described a murine model of malnutrition that mimicked features of moderate human malnutrition, and led to increased dissemination of Leishmania donovani. In this study, we investigated the effect of malnutrition on macrophage production of cytokines, prostaglandins (PGs), and leukotrienes (LTs). Using either LPS or calcium ionophore A23187 as a stimulus, macrophages from the malnourished mice produced a 3-fold higher PG/LT ((PGE₂+6-keto-PGF_1α)/(LTB₄+cysteinyl leukotrienes)) ratio than macrophages from well-nourished mice. LPS-stimulated macrophages from the malnourished mice produced decreased levels of TNF-α, GM-CSF, and IL-10, but similar levels of IL-6 and NO compared to well-nourished mice. A complex crosstalk between the eicosanoids and cytokines in the LPS-stimulated macrophages from the malnourished mice was evident by the following: (1) high levels of PG secretion despite low levels of TNF-α; (2) supplemental IL-10 modulated the excessive PG production; (3) GM-CSF rectified the PG/LT ratio, but did not correct the abnormal cytokine profile; and (4) inhibitors of cyclooxygenase decreased the PG/LT ratio, but did not affect TNF-α. Thus, in this model of malnutrition, there is a relative increase in anti-inflammatory PGs compared to pro-inflammatory LTs, which may contribute to immunodeficiency.     

Effect of malnutrition on rotavirus infection in suckling mice: kinetics of early infection

The effects of malnutrition on the viral replication pattern and severity of clinical disease were examined in suckling mice infected with mouse rotavirus (MRV). The infection in malnourished animals was characterized by a significant decrease in the minimal infectious dose and in the incubation period of the onset of diarrhea, when compared to well-nourished controls. Viral replication in the dispersed enterocytes was observed 6-12 hr earlier, fecal viral shedding peaked significantly earlier, and the clinical disease appeared to be more severe in the malnourished animals than in the controls. These observations provide strong evidence for malnutrition-induced alterations in the pathogenesis of rotaviral infection in vivo.     

Enumeration of micronucleated CD71-positive human reticulocytes with a single-laser flow cytometer

The extreme rarity of micronucleated reticulocytes (RETs) in the peripheral blood of non-splenectomized humans has precluded facile enumeration of these cells, as well as evaluation of this endpoint as an index of cytogenetic damage. In this report, we describe a high-throughput, single-laser flow cytometric system for scoring the incidence of micronuclei (MN) in newly formed human RETs. The procedure is based on an immunochemical reagent that differentially labels the most immature fraction of RETs from mature erythrocytes based on the expression level of the transferrin receptor (also known as CD71). The resolution of four erythrocyte populations (young RETs and mature erythrocytes, with and without MN) was achieved for human blood cells treated with phycoerythrin-conjugated anti-CD71, RNase, and either SYTOX Green or SYBR Green I nucleic acid dyes. Anti-glycophorin A labeling of erythroid cells (CyChrome conjugate) was also incorporated into the staining procedure to ensure that debris or other potential artifacts did not adversely impact the analyses. Instrument calibration procedures utilizing malaria-infected rodent erythrocytes were also developed, and are described. Using this analytical system, blood samples from 10 healthy non-splenectomized human volunteers were analyzed for micronucleus frequencies with a single-laser flow cytometer. Average micronucleus frequencies in the mature and most immature fraction of RETs were 0.016 and 0.19%, respectively. Blood samples from three healthy splenectomized volunteers were also evaluated. As expected, these samples exhibited higher micronucleus frequencies in the mature subset of erythrocytes (range 0.03-0.18%). The resulting data suggest that MN can be quantified in human erythrocyte populations with a single-laser flow cytometer, and that the frequency of MN cells in the youngest reticulocyte population approaches values expected in the absence of splenic selection against MN-erythrocytes. This high throughput system is potentially important for evaluating the value of the micronucleated reticulocyte endpoint as an index of chromosome breakage and/or chromosome segregational abnormalities in human populations.     

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.     

Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level

Background

In sub-Saharan Africa, preschool children represent the population most vulnerable to malaria and malnutrition. It is widely recognized that malnutrition compromises the immune function, resulting in higher risk of infection. However, very few studies have investigated the relationship between malaria, malnutrition and specific immunity. In the present study, the anti- Plasmodium falciparum IgG antibody (Ab) response was evaluated in children according to the type of malnutrition.

Methods

Anthropometric assessment and blood sample collection were carried out during a cross-sectional survey including rural Senegalese preschool children. This cross-sectional survey was conducted in July 2003 at the onset of the rainy season. Malnutrition was defined as stunting (height-for-age <-2 z-scores) or wasting (weight-for-height <-2 z-scores). The analysis was performed on all malnourished children in July (n = 161, either stunted, n = 142 or wasted, n = 19), pair-matched to well-nourished controls. The IgG Ab response to P. falciparum whole extracts (schizont antigens) was assessed by ELISA in sera of the included children.

Results

Both the prevalence of anti-malarial immune responders and specific IgG Ab levels were significantly lower in malnourished children than in controls. Depending on the type of malnutrition, wasted children and stunted children presented a lower specific IgG Ab response than their respective controls, but this difference was significant only in stunted children (P = 0.026). This down-regulation of the specific Ab response seemed to be explained by severely stunted children (HAZ ≤ -2.5) compared to their controls (P = 0.03), while no significant difference was observed in mildly stunted children (-2.5 < HAZ <-2.0). The influence of child malnutrition on the specific anti- P. falciparum Ab response appeared to be independent of the intensity of infection.

Conclusion

Child malnutrition, and particularly stunting, may down-regulate the anti- P. falciparum Ab response, both in terms of prevalence of immune responders and specific IgG Ab levels. This study provides further evidence for the influence of malnutrition on the specific anti-malarial immune response and points to the importance of taking into account child malnutrition in malaria epidemiological studies and vaccine trials.     

Copper, Iron, and Zinc Status in Children with Moderate and Severe Acute Malnutrition Recovered Following WHO Protocols

INTRODUCTION: The prevalence of copper, iron, and zinc deficiencies in malnutrition and the amounts of micronutrients that should be provided for nutritional recovery are unclear. OBJECTIVE: This study aims to measure (1) the frequency of Cu, Fe, and Zn deficiencies in children with acute malnutrition on day 1 and after 15- and 30-day treatments with F100 plus vitamins/minerals mix, and (2) anthropometric recovery after 30 d feeding ad libitum. METHODS: In Cochabamba, Bolivia, 12 hospitalized children with severe acute malnutrition (HSM) and 17 (hospitalized) with moderate acute malnutrition (HMM), 3-33 months, received F100 ad libitum for 1 month. Children received FeSO4 after infection subsided. On days 1, 15, and 30 weight, length, hemoglobin, serum ferritin, iron, copper, zinc, and ceruloplasmin were measured. Comparison group were 17 ambulatory moderately malnourished (AMM) and 34 well-nourished children, measured once. RESULTS: Deficiencies were highly prevalent in hospitalized groups. Serum copper and zinc became normal on D15 and D30, respectively. Mean daily energy intake of 160 kcal and 4 g prot//kg/d/1 mo led children to gain (mean) 5 g/kg/day, both on D15 and D30. CONCLUSIONS: Micronutrient deficiencies were highly prevalent in HSM and HMM and recovered similarly. Application of WHO protocols induced satisfactory copper status recovery, but improvement of zinc was slower.     

Proliferation index in bone marrow cells from severely malnourished rats during lactation.

The aim of this study was to determine if severe malnutrition affects the proportion of proliferating bone marrow cells in malnourished rats during lactation. Sister chromatid staining of metaphases was used as a parameter, as well as the morphology, size and color of bromodeoxyuridine labeled interphase nuclei. The BrdU proliferation labeling index was statistically lower in malnourished rats (20.4%), than in well-nourished controls (35.1%). A difference was also found between the two groups in the proportion of metaphases in first, second and third or successive cell cycle. The average generation time was longer in the malnourished group: 15.3 h, against 11.8 h for the controls. These results indicate that severe malnutrition affects both the proportion of bone marrow proliferating cells and their cell kinetics.     

Moderate and severe malnutrition alters proliferation of spleen cells in rats

Objectives

Previous studies have shown alterations in bone marrow cell proliferation in malnourished rats, during lactation. The objective of this study was to determine in vivo effects of moderate and severe malnutrition on spleen cell proliferation in 21‐day‐old rat pups.

Materials and methods

Spleen cell proliferation was determined following administration of bromodeoxyuridine (BrdUrd) over a time course of 2, 4, 6 and 8 h. Incorporation of BrdUrd was detected using FITC‐conjugated anti‐BrdUrd monoclonal antibodies and total DNA content was detected and evaluated using propidium iodide using flow cytometry.

Results

Proportions of cells in S and G₂/M were reduced in the rats with moderate (MN2^nd) and severe (MN3^rd) malnutrition. BrdUrd incorporation was lower in both groups of malnourished rat. In cells of MN2nd individuals, length of G₁ became shorter, while length of S‐phase increased. In contrast, fraction of cells in proliferation was significantly lower in both groups of malnourished rat, with MN3rd group having lowest percentage of cell population growth. In this study, severe malnutrition did not significantly affect duration of phases of the cell cycle, although fractions of proliferating cells were dramatically reduced.

Conclusion

Moderate malnutrition increased time of cells in DNA synthesis and time of total cell cycle and severe malnutrition reduced growth fraction of spleen cells in malnourished rats during lactation.

     

Frequency of sister-chromatid exchange (SCE) in bone-marrow cells of severely malnourished animals during early life

The frequency of sister-chromatid exchange (SCE) was examined in bone-marrow cells of 21-day-old Wistar rats malnourished during lactation and well-nourished controls of the same age. Malnutrition was obtained by increasing the litter size to 15 pups per mother. SCE were scored in 25 consecutive second-division metaphases in the femoral bone marrow cells from each animal. The average SCE in the malnourished animals was significantly higher than in the control group (p less than 0.01). The distribution of SCE per mitosis was also significantly higher in the malnourished animals (p less than 0.001). These results indicate that malnutrition per se during early life can increase SCE in the bone marrow of experimental animals.     

Frequency of sister chromatid exchanges in severe protein calorie malnutrition.

Nine children with severe protein calorie malnutrition were studied regarding the frequency of sister chromatid exchanges (SCE's) in peripheral blood lymphocytes. The results showed that there was no significant difference between the number of SCE's in the malnourished children as compared to an adequate control group. An interesting finding was that the proportion of 3rd or subsequent division metaphases found in the malnourished children, was higher and significantly different from that seen in the control group.     

Cryptosporidium-malnutrition interactions: mucosal disruption, cytokines, and TLR signaling in a weaned murine model

Cryptosporidiosis is a leading cause of persistent diarrhea in children in impoverished and developing countries and has both a short- and long-term impact on the growth and development of affected children. An animal model of cryptosporidial infection that mirrors closely the complex interaction between nutritional status and infection in children, particularly in vulnerable settings such as post-weaning and malnourishment, is needed to permit exploration of the pathogenic mechanisms involved. Weaned C57BL/6 mice received a protein-deficient (2%) diet for 3-12 days, then were infected with 5 × 10(7) excysted C. parvum oocyts, and followed for rate of growth, parasite stool shedding, and intestinal invasion/morphometry. Mice had about 20% reduction in weight gain over 12 days of malnutrition and an additional 20% weight loss after C. parvum challenge. Further, a significantly higher fecal C. parvum shedding was detected in malnourished infected mice compared to the nourished infected mice. Also, higher oocyst counts were found in ileum and colon tissue samples from malnourished infected mice, as well as a significant reduction in the villous height-crypt depth ratio in the ileum. Tissue Th1 cytokine concentrations in the ileum were significantly diminished by malnutrition and infection. mRNA for toll-like receptors 2 and 4 were diminished in malnourished infected mice. Treatment with nitazoxanide did not prevent weight loss or parasite stool shedding. These findings indicate that, in the weaned animal, malnutrition intensifies cryptosporidial infection, while cryptosporidial infection further impairs normal growth. Depressed TLR2 and 4 signaling and Th1 cytokine response may be important in the mechanisms underlying the vicious cycle of malnutrition and enteric infection.     

Micronucleated erythrocyte frequency in control and azidothymidine-treated Tk+/+, Tk+/- and Tk-/- mice

The first step in the activation of the anti-retroviral nucleoside analogue azidothymidine (AZT) involves its conversion to a 5′-monophosphate. In this study, we have evaluated the role of cytosolic thymidine kinase (Tk), the major enzyme involved in phosphorylating thymidine and its analogues, in the nuclear DNA damage produced by AZT in neonatal mice. Tk^+/+, Tk^+/− and Tk^−/− mice were treated intraperitoneally with 200 mg/kg/day of AZT on postnatal days 1 through 8, and micronuclei were measured in peripheral blood 24 h after the last dose. AZT treatment increased the micronucleus (MN) frequencies to similar extents in both the reticulocytes (RETs) and normochromatic erythrocytes (NCEs) of Tk^+/+ and Tk^+/− mice; AZT did not increase the frequency of micronucleated RETs (MN-RETs) or micronucleated NCEs (MN-NCEs) in Tk^−/− mice. Unexpectedly, neonatal Tk^−/− mice treated with the vehicle had significantly elevated MN frequencies for both RETs and NCEs relative to Tk^+/+ and Tk^+/− mice (e.g., 3.4% MN-RETs and 4.8% MN-NCEs in Tk^−/− mice versus 0.7 and 0.6% MN-RETs and MN-NCEs in neonatal Tk^+/+ mice). Additional assays performed on untreated Tk^−/− mice showed that elevated spontaneous MN frequencies persisted until at least 20 weeks of age, which approaches the average lifespan of Tk^−/− mice. These results indicate that metabolism by Tk is necessary for the genotoxicity of AZT in neonatal mice; however, the genotoxicity of AZT is not altered by reducing the Tk gene dose by half. The elevated spontaneous MN frequencies in Tk^−/− mice suggest the presence of an endogenous genotoxic activity in these mice.     

Increased susceptibility to metabolic alterations in young adult females exposed to early malnutrition

Early malnutrition during gestation and lactation modifies growth and metabolism permanently. Follow up studies using a nutritional rehabilitation protocol have reported that early malnourished rats exhibit hyperglycemia and/or hyperinsulinemia, suggesting that the effects of early malnutrition are permanent and produce a "programming" effect on metabolism. Deleterious effects have mainly been observed when early-malnutrition is followed by a high-carbohydrate or a high-fat diet.The aim of this study was to evaluate whether following a balanced diet subsequent to malnutrition can deter the expression of metabolic disease and lead rats to exhibit metabolic responses, similar to those of well-nourished controls.Young rats, born from dams malnourished during gestation and lactation with a low protein diet, were provided with a regular balanced chow diet upon weaning. At 90 days of age, the effects of rehabilitation were determined under three different feeding conditions: ad libitum, fasting or fasting-reefed satiated.Early-malnourished rats showed an increased rate of body weight gain. Males under ad libitum conditions showed an elevated concentration of hepatic glycogen and low values of insulin. In the fasting-reefed satiated condition, only early-malnourished females showed an alteration in glucose response and glucagon level, compared with their well-nourished controls.Data indicate that a balanced diet along life after early malnutrition can mask the expression of metabolic disorders and that a metabolic challenges due to a prolonged fasting and reefed state unmask metabolic deficiencies in early-malnourished females.     

Clinical Characteristics,Etiology and Antimicrobial Susceptibility among Overweight and Obese Individuals with Diarrhea: Observed at a Large Diarrheal Disease Hospital,Bangladesh

Background

The present study aimed to determine the clinical characteristics and etiology of overweight and obese (OO) individuals with diarrhea attending an urban Dhaka Hospital, International Centre for Diarrheal Disease Research (icddr,b), Bangladesh.

Methods

Total of 508 under-5 children, 96 individuals of 5–19 years and 1331 of >19 years were identified as OO from the Diarrheal Disease Surveillance System (DDSS) between 1993–2011. Two comparison groups such as well-nourished and malnourished individuals from respective age stratums were selected.

Results

Isolation rate of rotavirus was higher among OO under-5 children compared to malnourished group (46% vs. 28%). Rotavirus infection among OO individuals aged 5–19 years (9% vs. 3%) (9% vs. 3%) and >19 years (6% vs. 4%) (6% vs. 3%) was higher compared to well-nourished and malnourished children. Conversely, Vibrio cholerae was lower among all OO age groups compared to well-nourished and malnourished ones. Shigella (4% vs. 6%) (4% vs. 8%), and Campylobacter (3% vs. 5%) (3% vs. 5%) were lower only among OO in >19 years individuals compared to their counterparts of the same age stratum. Salmonella was similarly isolated in all age strata and nutritional groups. In multinomial logistic regression among under-5 children, significant association was observed only with use of antimicrobials at home [OR-1.97] and duration of hospital stay [OR-0.68]. For individuals aged 5–19 years, use of antimicrobials at home (OR-1.83), some or severe dehydration (OR-3.12), having received intravenous saline (OR-0.46) and rotavirus diarrhea (OR-2.96) were found to be associated with OO respectively. Moreover, significant associations were also found for duration of diarrhea before coming to hospital (>24 hours) (OR-1.24), Shigella (OR-0.46), and Campylobacter (OR-0.58) among >19 years OO individuals along with other associated co-variates in 5–19 years group (all p<0.05).

Conclusion and significance

Higher proportion of OO were infected with rotavirus and a greater proportion of them used antimicrobials before coming to the hospital.     

The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c⁺dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2⁺ macrophages, and CD169⁺ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system.     

A rationale for administering leukocyte endogenous mediator to protein malnourished,hospitalized patients

Leukocyte endogenous mediator is a low molecular-weight protein synthesized by circulating monocytes and fixed macrophages of the reticuloendothelial system. Exogenous administration of leukocyte endogenous mediator to a well-nourished animal stimulates both specific and nonspecific immune function and replicates the protein metabolic response to infection, characterized by fever and increased amino acid oxidation, skeletal protein degradation and synthesis of “acute-phase” proteins. Leukocyte endogenous mediator administration also affords protection against semilethal doses of bacteremia in the well-nourished animal.In the protein-depleted host, synthesis or release of leukocyte endogenous mediator in response to infection appears to be reduced and the attenuated metabolic response may be attributed, in part, to a deficit in its production. However, nutritional repletion of the malnourished patient results in restoration of the capacity to produce leukocyte endogenous mediator usually within three to seven days, if adequate dietary protein is provided.Since protein malnutrition is associated with increased incidence and severity of bacterial infections, we postulate that the reduced synthesis and/or release of leukocyte endogenous mediator in protein malnutrition is detrimental. In those critically-ill, malnourished patients who cannot endogenously synthesize leukocyte endogenous mediator, and for clinical reasons cannot be repleted rapidly or are already infected and/or undergoing operative stress, exogenous administration of leukocyte endogenous mediator should be considered along with nutritional support. Administration of this protein to a seriously-ill malnourished individual should produce a metabolic profile of fever, increased urinary nitrogen excretion and falls in serum albumin concentrations that are generally considered pathologic. However, administration of leukocyte endogenous mediator over short periods of time should also provide the anabolic impetus for the augmented synthesis of proteins beneficial to recovery. In most cases, these countervailing forces of anabolism and catabolism should be of benefit to the host if the response to infection and injury is viewed as a physiologic redistribution of endogenous nutrients to meet the more critical and immediate needs of the stressed patient.