The effect of 17ß-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model.

Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17ß-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17ß-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition.

BACKGROUND: We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). OBJECTIVE: We tested the hypothesis that methionine supplementation may increase protein-derived cysteine and upregulate cysteine synthesis, thereby improving glutathione synthesis during the early treatment of edematous SAM. DESIGN: The cysteine flux, its de novo synthesis and release from protein breakdown, and erythrocyte glutathione synthesis rate were measured in 12 children with edematous SAM in the fed state by using stable isotope tracers at 3 clinical phases as follows: 3 ± 1 d (±SE) [clinical phase 1 (CP1)], 8 ± 1 d [clinical phase 2 (CP2)], and 14 ± 2 d (clinical phase 3) after admission. Subjects were randomly assigned to receive equimolar supplements (0.5 mmol ⋅ kg(-1) ⋅ d(-1)) of methionine or alanine (control) immediately after CP1. RESULTS: In the methionine compared with the alanine group, cysteine flux derived from protein breakdown was faster at CP2 than CP1 (P < 0.05), and the change in plasma cysteine concentration from CP1 to CP2 was greater (P < 0.05). However, there was no evidence of a difference in cysteine de novo synthesis and its total flux or erythrocyte glutathione synthesis rate and concentration between groups. CONCLUSIONS: Methionine supplementation increased cysteine flux from body protein but had no significant effect on glutathione synthesis rates. Although cysteine is made from methionine, increased dietary cysteine may be necessary to partially fulfill its demand in edematous SAM because glutathione synthesis rates and concentrations were less than previous values shown at full recovery. This study was registered at clinicaltrials.gov as NCT00473031.

Kwashiorkor from a severe dietary restriction in an 8-month infant in suburban Detroit, Michigan: case report and review of the literature.

Kwashiorkor is a type of protein-calorie malnutrition often seen in children of impoverished countries and famine. The condition occurs in the setting of insufficient protein intake in the presence of sufficient caloric intake. We report a case of a 8-month-old male infant in the suburban Detroit, MI, USA who presented with diffuse edema, erythroderma and desquamation, a "bull-dog" face, diarrhea, and irritability, consistent with kwashiorkor as a result of severe dietary restriction. The mother had placed the child on a severely restrictive diet, consisting only of RICE DREAM((R)) milk, sweet potatoes and bananas, with the assumption that it would help his rash. Nineteen prior cases of kwashiorkor induced in infants by dietary restriction of "well intending" parents have been reported in the US literature. Malnutrition is often under diagnosed or misdiagnosed in developed countries such as the United States. The results, if unrecognized or untreated, may be devastating. This makes it imperative that physicians consider this diagnosis, recognize potential risk factors and be prepared to accurately assess overall nutritional status of patients.

Clinical evaluation of Acalypha ointment in the treatment of superficial fungal skin diseases.

In an open non-comparative study to evaluate the efficacy and safety of Acalypha wilkesiana ointment in superficial fungal skin diseases, 32 Nigerian patients with clinical and mycological evidence of superficial mycoses were recruited. Twelve patients defaulted and were lost to follow up, while one patient withdrew because of intolerable excoriation at the site of the lesion. Of the 19 patients that completed the trial, clinical cure was achieved in 73.3% of the patients. The ointment was very efficacious in the treatment of Tinea pedis, Pityriasis versicolor and Candida intetrigo where the cure rate was 100% in each condition. It is recommended that Acalypha ointment can be used for the treatment of these superficial mycoses.

Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition.

BACKGROUND: Children with severe edematous malnutrition have higher than normal oxidant damage and lower concentrations of the antioxidant reduced glutathione (GSH), which are associated with slower synthesis of GSH and with low extra- and intracellular concentrations of the precursor amino acid cysteine. OBJECTIVE: We tested whether early dietary supplementation with cysteine could restore a normal GSH concentration and synthesis rate in these children. DESIGN: Erythrocyte cysteine and GSH concentrations and the fractional and absolute synthesis rates of GSH were measured in 2 groups of 16 edematous malnourished children, 10 boys and 6 girls aged 6-18 mo, at 3 times after hospital admission: at approximately 2 d (period 1), when they were malnourished and infected; at approximately 11 d (period 2), when they were malnourished but cleared of infection; and at approximately 50 d (period 3), when they had recovered. Supplementation with either 0.5 mmol. kg(-1). d(-1) N-acetylcysteine (NAC group) or alanine (control group) started immediately after period 1 and continued until recovery. RESULTS: From period 1 to period 2 the concentration and the absolute synthesis rate of GSH increased significantly (P < 0.05) in the NAC group but not in the control group. The increases in the GSH concentration and synthesis rate were approximately 150% and 510% greater, respectively, in the NAC group than in the control group. The increases in the NAC group were associated with a significant effect of supplement (P < 0.03) on erythrocyte cysteine concentration. CONCLUSION: These results suggest that the GSH synthesis rate and concentration can be restored during the early phase of treatment if patients are supplemented with cysteine.

Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings.

Role of micronutrients namely vitamin A, zinc and folate, as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy. Apart from a selective review, attempts have been made to statistically combine results of several studies to address policy issues. In children, vitamin A supplementation during illness has (a) a profound effect in reducing mortality in measles, (b) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea, and (c) no benefit in pneumonia. Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia. Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture. Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly, bulging fontanelle observed in infants when co-administered at immunization. In children, zinc supplementation during illness, (a) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea, (b) resulted in reduced rate of treatment failure and death in persistent diarrhea, (c) had no effect in measles and non-measles pneumonia, and (d) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children. The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further. Concerning policy, zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea. However, recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness, cost, operations and safety. In two randomized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect. Folate is not recommended as adjunct therapy of diarrhea. Role of folate in preventing severe disease and/or death deserves further evaluation.

[Effects of vitamin A supplementation on nutritional markers on the follow-up of malnutrition in children]. / Effets de la supplémentation en vitamine A sur les marqueurs de la nutrition dans la prise en charge de la malnutrition de l'enfant.

Prospectively assessment of vitamin A supplemented during a follow-up of a protein-energy malnutrition rehabilitation included serum retinol, Retinol Binding Protein (RBP) and prealbumin (PA) determination. This study was conducted during one month on a group of 36 vitamin A (200,000 IU) supplemented malnourished children and 32 age-and sex-matched malnourished children receiving only a nutritional regimen. Determinations were carried out at days 0, 15 and 30. Protein marker concentrations increased steadily in supplemented children as compared to those in the untreated group (p < 0.05, Student's t test). On the other hand, serum concentrations of the two proteins progressively regained normal values in the vitamin A supplemented group. Data also showed that retinol supplementation in conjunction with an appropriate nutritional diet is effective in raising serum concentrations of vitamin A and its binding proteins to normal levels. Therefore, we concluded that the results of this study demonstrates the importance of vitamin A supplementation in the management of these deficiency states.

Potassium supplementation in kwashiorkor.

BACKGROUND: Kwashiorkor is an edimatous form of severe malnutrition and is the predominant form of childhood malnutrition in Malawi. Potassium depletion is common and contributes to the high mortality. The aim of this study was to determine if high potassium supplementation improves the outcome of kwashiorkor treatment. METHODS: We performed a randomised, double-blind, placebo-controlled, clinical trial of high potassium supplementation in 99 children with kwashiorkor. Controls (n = 51) received a standard potassium intake of 4.7 mmol/kg/day. The intervention group (n = 48) received 7.7 mmol/kg/day. All cases (intervention and control groups) were treated in the hospital-based Nutrition Rehabilitation Center and received a standard treatment regime of mild feeds, mineral and vitamin supplements, and antibiotics. RESULTS: There was no significant difference in length of hospitalization, or time for resolution of oedema between groups. The case-fatality rate was reduced by 33% in the high potassium intervention group (13/48) compared to controls (21/51). There was a significant reduction in late deaths (13 in controls vs 3 in intervention group; odds ratio 5.3, 95% confidence interval 1.2-31.0) but no difference in early deaths (0-5 days). The intervention group also had significantly fewer presumed septic episodes (3 vs 18, odds ratio 8.9, confidence interval 2.2-50.9), respiratory symptoms, and new skin ulcerations than controls. CONCLUSIONS: The high potassium supplementation reduced mortality and significant morbidity in kwashiorkor. This may be due to improved myocardial and immune function from earlier repletion of intracellular potassium. We recommend that the standard potassium supplement for the initial phase of treatment of kwashiorkor be increased from 4 to 8 mmol/kg/day.

[Vitamin e supplementation in Senegalese children with kwashiorkor]. / Supplémentation en vitamine E chez des enfants sénégalais présentant un kwashiorkor.

Kwashiorkor continues to be a major cause of infant mortality in the developing world. It has recently been suggesting that this form of malnutrition is due to oxidizing aggression. Vitamin E is a powerful natural anti-oxidant, and we therefore investigated the extent to which its supplementation in the diet contributed to treating child kwashiorkor. Vitamin E was also administered to children suffering from marasmus. The study was conducted from October 1993 to July 1994 and included 79 children (38 cases of kwashiorkor and 41 of marasmus). The treatment resulted in a 76% success rate, with the best results for marasmus (89.5% cure). However, the supplement did not have any effect on the nutritional status for either the kwashiorkor or marasmus patients. In the kwashiorkor group, the weight increase, after disappearance of edema was 15.2 +/- 4.9 g/kg/d in the supplemented group as compared to 16.4 +/- 3.6 g/kg/d in the control group. The duration of edema along treatment was similar for the two groups (supplemented: 8.6 +/- 3.1 days, control group: 7.1 +/- 3.9 days). Possible reasons for vitamin E supplementation having no effect are discussed.

PIP: 38 children with kwashiorkor and 41 with marasmus participated in a study of vitamin E supplementation in a nutritional rehabilitation center in the Dakar suburb of Pikine. Kwashiorkor, or edematous malnutrition, is a major factor in infant mortality in Senegal. Vitamin E supplementation was undertaken to test the hypothesis that kwashiorkor results from aggressive oxidation linked to excess free radicals, vitamin E being a major antioxidant in humans. The children attended the center daily, accompanied by their mothers, until they were cured, defined as disappearance of edema and achievement of 80% of the international standard of weight for height. All children were treated for parasites and malaria prevention. Children with kwashiorkor were given ampicillin, metronidazole and supplements of particular minerals. Between October 1993 and July 1994, 17 children with kwashiorkor and 19 with marasmus were given the vitamin E supplements, the other 43 children serving as controls. The cure rate was slightly higher for the groups receiving supplements, but the difference was not statistically significant. The highest cure rate, 89.5%, was in children with marasmus receiving the supplement, and the lowest cure rate, 68.2%, was in control children with marasmus, but the difference was not statistically significant. Among children with kwashiorkor, weight gain after disappearance of edema was 15.2 +or- 4.9 g/kg/d in the vitamin E group and 16.4 +or- 3.6 g/kg/d in the control group. Several factors may explain the absence of a favorable effect of vitamin E. The hypothesized relationship between aggressive oxidation and kwashiorkor may not exist, or the low plasma levels of vitamin E may not truly reflect deficiencies at the tissue level. The treatment dose of 10 mg/d of vitamin E may have been too low, or the existence of multiple deficiencies may have masked the possible beneficial effect of vitamin E.

Pharmacokinetics of amikacin in children with kwashiorkor.

The pharmacokinetics of intravenous amikacin, administered as a mean (SD) bolus dose of 5.5 (1.2) mg/kg to children between the ages of 1 and 4 years with kwashiorkor, was studied. Although there was a tendency for the average volume of distribution to increase to the upper limit of normal, plasma elimination half-life, first order elimination-phase rate constant and clearance remained close to the reference values for adults. Despite marginal elevation of the average t1/2 beta-value, reflecting a general trend, renal impairment in respect of amikacin clearance could not be demonstrated. It was concluded that the changes in pharmacokinetic parameters found in kwashiorkor are not large enough to amend the current therapeutic regimens for amikacin in this condition.

[Selenium, an essential and toxic element. Latin American data]. / Selenio, un elemento esencial y tóxico. Datos de Latinoamérica.

After a brief discussion of some of the aspects of importance, sources, deficiencies and excesses of selenium the great differences of ingestion between different countries are mentioned. Breast fed children from an area in Venezuela ingest 10 times the amount compared with children from Finland. Among sesame seed samples from 20 different countries used as Se indicators, the highest and the lowest values were found in those of Latin-American origin. With very few exceptions the highest and the lowest urinary and serum Se levels reported in the literature came from this region. The performance of more studies in Latin-America on Se is recommended. Urinary excretion and analysis of finger nails or egg-white of freely foraging hens could be used as suitable indicators.

Effects of cortisol and growth hormone on the metabolism of liver and bone in children with malnutrition.

A protein-energy deficit produces stress in the organism affecting all systems. Proportional to the degree of disease, cortisol and GH are mostly responsible for some of these effects. To investigate the effects on liver and bone, cortisol, GH, AST, ALT, ALP activities and Ca(T) and P(i) in serum were measured in 21 marasmus, nine kwashiorkor and 34 control children. In the marasmus group, we found a positive correlation between cortisol and AST, ALT and Ca(T) and a negative correlation between cortisol and ALP. In the kwashiorkor group there were positive correlations between the same parameters, although, they were of a lesser degree. Furthermore, in the kwashiorkor group we established a positive correlation between GH and ALP. Cortisol stimulates transaminases directly and suppresses ALP activity, thus indirectly increasing Ca(T), whereas GH has no direct effect on these enzymes. As the disease progresses and as liver functions deteriorate, AST, ALT and ALP increase in serum.

Effacement of glomerular foot processes in kwashiorkor.

In a study of the pathogenesis of the oedema of kwashiorkor the ultrastructure of the kidneys from 6 children was examined shortly after they died from oedematous malnutrition. There was a generalised effacement of the glomerular epithelial cells onto the basement membrane. The filtration slits that remained were narrowed. The picture was similar to that seen in minimal-change nephrotic syndrome--but none of the children had albuminuria. The degree of effacement was statistically related to treatment with gentamicin. The findings suggest that there is a defect in the anionic charge of the glomerular basement membrane in oedematous malnutrition, that the membrane charge is more easily neutralised by cations such as gentamicin, and that, because proteinuria is not a feature of oedematous malnutrition, the proteinuria in other conditions associated with glomerular epithelial cell effacement (eg, minimal-change nephrotic syndrome) is due to something more complex than simple loss of charge.

Effacement of glomerular foot processes in kwashiorkor

In a study of the pathogenesis of the oedema of kwashiorkor the ultrastructure of the kidneys from 6 children was examined shortly after they died from oedematous malnutrition. There was a generalised effacement of the glomerular epithelial cells onto the basement membrane. The filtration slits that remained were narrowed. The picture was similar to that seen in minimal-change nephrotic syndrome-but none of the children had albuminuria. The degree of effacement was statistically related to treatment with gentamicin. The findings suggest that there is a defect in the anionic charge of the glomerular basement membrane in oedematous malnutrition, that the membrane charge is more easily neutralised by cations such as gentamicin, and that, because proteinuria is not a feature of oedematous malnutrition, the proteinuria in other conditions associated with glomerular epithelial cell effacement (eg, minimal-change nephrotic syndrome) is due to something more complex than simple loss of charge.(AU)

Improvement in plasma protein concentrations with fibronectin treatment in severe malnutrition.

Severely malnourished young children (n = 72) were treated with intravenous fibronectin to assess its efficacy as an adjunct treatment for kwashiorkor and/or marasmus. The protein was given in a double-blind study during the first 4 d of hospitalization together with standard nutrition and supportive therapy. Fibronectin concentrations as well as albumin, transferrin, prealbumin, and alpha-2-macroglobulin were monitored in samples taken before each dose of fibronectin and in samples taken five times thereafter. Sick individuals had significantly lower concentrations of all five proteins than did healthy control individuals of matching ages. Mean fibronectin concentrations were 98 +/- 7 mg/L (mean +/- SEM) for sick vs 303 +/- 21 mg/L for healthy individuals. Concentrations of all five proteins increased at a greater daily rate in patients treated with fibronectin than in patients who received placebos. Eighty-seven percent of the treated children survived to the end of the treatment and observation periods (mean hospitalization 14.7 d) whereas only 56% of the control subjects survived (P = 0.004). These data support the use of intravenous fibronectin as an adjunct in the treatment of severe malnutrition at a dosage of 7.5 mg.kg-1.d-1 over a 4-d period.