Sustained hypophosphatemia after denosumab in a patient on hemodialysis.

An 81-year-old Caucasian man who had commenced thrice weekly hemodialysis (HD) three months earlier, presented with a hip fracture, two vertebral fractures and a bone mineral density T-score of -3.6. He had received weekly iron sucrose infusions for 6 weeks and alphacalcidol on dialysis days. Although he suffered from coeliac disease and cirrhosis, he was fully ambulatory and well-nourished. He was normocalcaemic with a marginally low plasma phosphate and the PTH was 11.8 pmol/L (<2-times the upper range of the assay). In view of his severe osteoporosis, it was decided to treat him with denosumab (dmab). Laboratory assessment 2 weeks post dmab showed severe hypophosphatemia and hypocalcemia; phosphate 0.11 mmol/L and ionized calcium 0.83 mmol/L, and he was admitted for intravenous phosphate infusion. Three months later he remained on a phosphate supplement. The case illustrates that, in addition to the risks of hypocalcemia in patients with kidney failure and high bone turnover, kidney failure patients without evidence of high bone turnover, can also be at risk of hypocalcemia and severe hypophosphatemia requiring acute hospitalization and phosphate infusion. The potential role of compromised phosphate absorption versus increased deposition will be discussed. We recommend a cautious approach to dmab therapy in patients on dialysis, with evaluation of bone turnover and serum phosphate levels prior to initiation of treatment.

Alanda (Ephedra foeminea) nanoparticles as a modulator of genomic DNA degradation in mice: new inspiration for treating Ehrlich solid tumour-induced kidney and liver toxicity.

OBJECTIVE: The limitations faced by conventional drug delivery systems are being overcome through the use of rapidly evolving cancer nanotherapeutics. Determining the manner in which the Ehrlich solid tumor (EST) is impacted by the new bioactive Alanda-loaded flax seed gum nanoparticles (Alanda NPs) functioning as an anti-carcinogenic agent represents the research objective of this paper. MATERIALS AND METHODS: Identification of the functional groups, surface morphology, particle size, and zeta potential were among the characterizations and preparations made for the prepared nanoparticles. A Control group, a Flax Seed Gum group, a raw Alanda group, an Alanda NPs group, an EST group, and an induced EST treated with Alanda NPs group comprised the six groups respectively which the 60 female mice were separated into in this in vivo study. RESULTS: Toxicity assessments for kidneys and liver were performed alongside the detection of total genomic DNA degradation. The zeta potential and the particle sizes for Alanda NPs were -25.60±0.38 mv and 40±0.28 nm, respectively, where the latter demonstrated a monodisperse spherical shape, per the findings. The use of Alanda NPs to treat EST was found to alle te the DNA damage, apoptosis, and renal and hepatic toxicity that EST induces. Additionally, the activation of oxidative stress and apoptosis causing the renal and hepatic toxicity induced by EST is counteracted by the scavenging of free radicals by the Alanda NPs. CONCLUSIONS: A high degree of safety for effective cancer treatment was displayed by the newly developed oral nanoparticles while also demonstrating strong potential in vivo.

Evaluation of hepatoprotective effect of Nebivolol and sodium copper Chlorophyllin on CCL4-induced hepatotoxicity in mice.

OBJECTIVE: In this study, the protective effect of sodium copper chlorophyllin and nebivolol was evaluated in a mice model of CCL4 induced hepatotoxicity. Silymarin was used as a traditional hepatoprotective drug. MATERIALS AND METHODS: Thirty (30) mice were used as they were divided into five groups: the first group was the control group which received distilled water + olive oil, the second group which received 1.5 ml/kg of CCl4 diluted in olive oil three times a week, the third group which received CCl4 + Silymarin 50 mg/kg/day, the fourth group which received CCl4 + nebivolol 4 mg/kg/day, and the fifth group which received 1.5 ml/kg of CCl4+ Cu-chlorophyllin 50 mg/kg/day. The drugs were given by intraperitoneal route for 5 weeks. The detection, quantification of CCl4 induced hepatotoxicity and possible protective effect of either silymarin, nebivolol, or sodium copper chlorophyllin were assessed using biochemical analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, lipid profile, an assay of oxidants and antioxidants, assay of interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-α), and histopathological examination. RESULTS: The administration of carbon tetrachloride (CCl4) produced pronounced liver impairment. It significantly increased ALT, AST, ALP, malondialdehyde, and serum nitric oxide levels compared to normal control group besides a decrease in total protein, serum catalase, tissue SOD, and GSH levels. IL-6 and TNF-α levels were significantly higher while total cholesterol was significantly lower in mice receiving CCL4 compared to the normal control group. CCL4 induced severe hyperemia and congestion inside the portal area with leukocytic infiltration, hepatic degeneration, and bridge fibrosis. CONCLUSIONS: Co-administration of either silymarin, nebivolol, or sodium copper chlorophyllin with CCl4 was able to ameliorate up to almost contradict CCl4 induced hepatic injury through their anti-inflammatory and antioxidant activities.

Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

Ultrastructure changes induced by the phloroglucinol derivative agrimol G isolated from Leucosidea sericea in Haemonchus contortus.

Plant extracts used for the treatment of helminth infections in sheep are an alternative to chemical anthelmintic drugs. Previous studies have reported the anthelmintic activity of acetone leaf extracts of Leucosidea sericea. For this study, we evaluate the ultrastructure changes induced by the acetone leaf extract of L. sericea and the component agrimol G (AG) that was isolated for the first time on adult haemonchus parasites. Adult haemonchus parasites harvested from sheep were incubated with the plant extract and AG for 3 h and evaluated by both scanning and transmission electron microscopy in comparison and in combination with albendazole or ivermectin. In all cases the method of evaluation shows ultrastructural changes, with albendazole inducing mitochondrial damage and ivermectin inducing muscle degeneration, both as previously described. Incubation with the plant extract and AG resulted in the formation of numerous non-membrane bound multi-vesicular like bodies and evenly spread disruptions/erosion in the epicuticle. Combining AG with ivermectin or albendazole resulted in an absence of effect of AG. Based on the structural changes induced by AG, together with the absence of an effect in combination with ivermectin and albendazole would suggest a disrupted microtubular network. The latter does however require biochemical confirmation.

Mechanism for prevention of infection in preterm neonates by topical emollients: a randomized, controlled clinical trial.

BACKGROUND: Topical applications of emollients such as sunflower seed oil and Aquaphor have been shown to reduce the incidence of bloodstream infections and mortality of preterm infants in resource-poor settings. The causal mechanism for prevention of infection through cutaneous portals of entry is not well understood. METHODS: We examined the relationship between skin condition score as a measure of skin barrier integrity and risk for bloodstream infection, and the effect of emollients on that relationship. Data for this study come from a randomized controlled trial of the impact of topical emollient therapy on nosocomial infections in 491 preterm infants <33 weeks gestational age at Dhaka Shishu Hospital, Bangladesh. Latent growth trajectory model with random-coefficient and multivariable logistic regression were utilized. RESULTS: Rate of deterioration of skin condition was significantly lower (P < 0.05) in both emollient arms compared with the untreated control group. Adjusted odds ratio of skin score for infection was 1.32 (95% confidence interval: 1.06-1.65). Emollients reduced the incidence of infection only when the skin had no signs of deterioration [Aquaphor incidence rate ratio: 0.43 (95% confidence interval: 0.19-0.97) and sunflower seed oil incidence rate ratio: 0.46 (95% confidence interval: 0.21-0.99)]. CONCLUSION: Skin condition deteriorated progressively after birth and compromised skin condition increased the risk of infection. Emollients preserved skin integrity and thus prevented infection in preterm neonates. To optimize benefits of emollients for the prevention of bloodstream infection, use of emollients should begin immediately after birth when the skin is still intact.

Cost-effectiveness of skin-barrier-enhancing emollients among preterm infants in Bangladesh.

OBJECTIVE: To evaluate the cost-effectiveness of topical emollients, sunflower seed oil (SSO) and synthetic Aquaphor, versus no treatment, in preventing mortality among hospitalized preterm infants (< 33 weeks gestation) at a tertiary hospital in Bangladesh. METHODS: Evidence from a randomized controlled efficacy trial was evaluated using standard Monte Carlo simulation. Programme costs were obtained from a retrospective review of activities. Patient costs were collected from patient records. Health outcomes were calculated as deaths averted and discounted years of life lost (YLLs) averted. Results were deemed cost-effective if they fell below a ceiling ratio based on the per capita gross national income of Bangladesh (United States dollars, US$ 470). FINDINGS: Aquaphor and SSO were both highly cost-effective relative to control, reducing neonatal mortality by 26% and 32%, respectively. SSO cost US$ 61 per death averted and US$ 2.15 per YLL averted (I$ 6.39, international dollars, per YLL averted). Aquaphor cost US$ 162 per death averted and US$ 5.74 per YLL averted (I$ 17.09 per YLL averted). Results were robust to sensitivity analysis. Aquaphor was cost-effective relative to SSO with 77% certainty: it cost an incremental US$ 26 more per patient treated, but averted 1.25 YLLs (US$ 20.74 per YLL averted). CONCLUSION: Topical therapy with SSO or Aquaphor was highly cost-effective in reducing deaths from infection among the preterm neonates studied. The choice of emollient should be made taking into account budgetary limitations and ease of supply. Further research is warranted on additional locally available emollients, use of emollients in community-based settings and generalizability to other geographic regions.

Effect of skin barrier therapy on neonatal mortality rates in preterm infants in Bangladesh: a randomized, controlled, clinical trial.

OBJECTIVE: Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. METHODS: A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care children's hospital in Bangladesh. Preterm infants (gestational age: < or = 33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. RESULTS: Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. CONCLUSIONS: Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries.

Acceptability of massage with skin barrier-enhancing emollients in young neonates in Bangladesh.

Oil massage of newborns has been practised for generations in the Indian sub-continent; however, oils may vary from potentially beneficial, e.g. sunflower seed oil, to potentially toxic, e.g. mustard oil. The study was carried out to gain insights into oil-massage practices and acceptability of skin barrier-enhancing emollients in young, preterm Bangladeshi neonates. Preterm infants of <33 weeks gestational age were randomized to high-linoleate sunflower seed oil, Aquaphor Original Emollient Ointment, or the comparison group (usual care). A survey was administered at admission to assess routine skin-care practices prior to admission and at discharge to assess acceptability of emollient therapy during hospitalization. Oil massage was given to 83 (21%) of 405 babies before hospital admission, 86% (71/83) of whom were delivered at home. Application of oil, most commonly mustard oil (88%, 73/83), was started within one hour of birth in 51 cases (61%) and was applied all over the body (89%, 74/83) one to six (mean 2.2) times before admission. Of infants who received emollient therapy in the hospital, 42% (n=32) of mothers reported that the emollient applied in the hospital was better than that available at home, and only 29% would use the same oil (i.e. mustard oil) in the future as used previously at home. No problems resulted from use of emollient in the hospital. Topical therapy with sunflower seed oil or Aquaphor was perceived by many families to be superior to mustard oil. If caregivers and health professionals can be motivated to use inexpensive, available emollients, such as sunflower seed oil that are beneficial, emollient therapy could have substantial public-health benefit.

Effect of topical emollient treatment of preterm neonates in Bangladesh on invasion of pathogens into the bloodstream.

Topical emollient therapy may reduce the incidence of serious infections and mortality of preterm infants in developing countries. We tested whether emollient therapy reduced the burden of pathogens on skin and/or prevented bacterial translocation. Neonates <33 wk gestational age were randomized to treatment with sunflower seed oil (SSO) or Aquaphor or the untreated control group. Skin condition score and skin cultures were obtained at enrollment and on d 3, 7, and weekly thereafter, and blood cultures were obtained for episodes of suspected nosocomial sepsis. For analysis, blood cultures were paired with skin cultures obtained 0-3 d before the blood culture. Skin condition scores at 3 d were better in patients treated with either emollient compared with untreated controls; however, skin flora was similar across the groups. The SSO group showed a 72% elevated odds of having a false-positive (FP) skin culture associated with a negative blood culture (i.e. skin flora blocked from entry into blood) compared with the control group. Topical therapy with SSO reduced the passage of pathogens from the skin surface into the bloodstream of preterm infants.

Ciprofloxacin treatment in preterm neonates in Bangladesh: lack of effects on growth and development.

BACKGROUND: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. OBJECTIVE: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. METHODS: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. RESULTS: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. CONCLUSIONS: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.

Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial.

BACKGROUND: Infections and complications of prematurity are main causes of neonatal mortality. Very low birthweight premature infants have compromised skin barrier function, and are at especially high risk for serious infections and mortality. Our aim was to ascertain whether topical application of emollients to enhance skin barrier function would prevent nosocomial infections in this population. METHODS: We randomly assigned infants born before week 33 of gestation after admission to Dhaka Shishu Hospital, Bangladesh, to daily massage with sunflower seed oil (n=159) or Aquaphor (petrolatum, mineral oil, mineral wax, lanolin alcohol; n=157). We then compared incidence of nosocomial infections among infants in these two groups with an untreated control group (n=181) by an intention-to-treat analysis. FINDINGS: 20 patients in the control group, and 22 in each of the treatment groups left the hospital early, but were included in the final analysis. Overall, infants treated with sunflower seed oil were 41% less likely to develop nosocomial infections than controls (adjusted incidence rate ratio [IRR] 0.59, 95% CI 0.37-0.96, p=0.032). Aquaphor did not significantly reduce the risk of infection (0.60, 0.35-1.03, p=0.065). No adverse events were seen. INTERPRETATION: Our findings confirm that skin application of sunflower seed oil provides protection against nosocomial infections in preterm very low birthweight infants. The low cost, availability, simplicity, and effect of treatment make it an important intervention for very low birthweight infants admitted to hospital in developing countries.

Anaemia among schoolchildren in Qena Governorate, Upper Egypt.

A study was carried out during January/February 2001 in Deshna and Armant Districts of Qena Governorate, Upper Egypt, to establish the prevalence of anaemia among schoolchildren aged 6 to 11 years and define appropriate control interventions in the area. Haemoglobin levels were measured directly in schools using a portable spectrophotometer. The mean (SD) level of haemoglobin in 1844 schoolchildren in 37 schools was 12.79 (1.15) g/dL. Only 12% of children were below the WHO cut-off for anaemia for this age group (< 11.5 g/dL) and no cases of severe anaemia (< 7.0 g/dL) were detected. The low prevalence of mild to moderate anaemia indicates that mass iron supplementation is not justifiable, but routine monitoring of haemoglobin levels should be part of the public health activities in the schools.

Anaemia among schoolchildren in Qena Governorate, Upper Egypt

A study was carried out during January/February 2001 in Deshna and Armant Districts of Qena Governorate, Upper Egypt, to establish the prevalence of anaemia among schoolchildren aged 6 to 11 years and define appropriate control interventions in the area. Haemoglobin levels were measured directly in schools using a portable spectrophotometer. The mean [SD] level of haemoglobin in 1844 schoolchildren in 37 schools was 12.79 [1.15] g/dL. Only 12% of children were below the WHO cut-off for anaemia for this age group [< 11.5 g/dL] and no cases of severe anaemia [< 7.0 g/dL] were detected. The low prevalence of mild to moderate anaemia indicates that mass iron supplementation is not justifiable, but routine monitoring of haemoglobin levels should be part of the public health activities in the schools

Quantification of absorbed doses to urine bladder depending on drinking water during radioiodine therapy to thyroid cancer patients: a clinical study using MIRDOSE3.

The object of the study was to quantify the absorbed doses to urinary bladder using MIRDOSE3 (medical internal radiation dose package program) depending on drinking water after giving radioiodine dose to thyroid cancer patients. Twenty-nine female thyroid cancer patients (aged 40-60 years, mean 50 years) were selected. The therapeutic doses ranged from 3700 to 7400 MBq of 131I. The radioiodine uptake was measured at 1 cm distance from three organs (previously marked), the thyroid, thigh and stomach, by using a calibrated Eberline ESP-2 GM counter, with a special arrangement of each patient. Urine samples were collected every 12 h for first 72 h, and then every 24 h for the next 96 h. The individual biological half-life of excreted urine was calculated using individual effective half-life. Absorbed doses were calculated for an adult female phantom using the dynamic bladder model of MIRDOSE3 program in two phases: firstly, for different voiding intervals; and secondly, depending on individual drinking water. An average of 85% of the total dose passed through the urinary tract within the first 72 h, with a biological half-life of 28.5+/-0.747 h, and 9% for the next 96 h with a biological half life of 118.43+/-0.645 h. The voiding interval shows great impact on total absorbed dose to bladder and water supplementation needs to be intensified to reduce absorbed doses to bladder wall for the first 3 days.

Isoflavonoid glycosides from Dalbergia sissoo.

Two isoflavone glycosides, biochanin A 7-O-[beta-D-apiofuranosyl-(1-->5)-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside] and tectorigenin 7-O-[beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside], were isolated from Dalbergia sissoo. Their structures were elucidated on the basis of spectral and chemical evidence.

Phenolic constituents from Grevillea robusta.

Seven phenolic compounds were isolated from a MeOH extract of the leaves of Grevillea robusta. Their structures were determined by various spectral methods including 2D NMR spectroscopy.

Influence of dietary mineral imbalance on the incidence of urolithiasis in Egyptian calves.

The influence of certain dietary elements on the urolithiasis syndrome in cattle calves was elucidated. Calcium, phosphorus, and magnesium measurements were conducted on feed rations as well as on serum and urine samples collected from affected and normal calves. Analysis of the rations given to the animals showed phosphorus at higher levels than calcium, indicating mineral imbalance. Serum and urine of urolithic calves were characterised by high phosphorus, calcium, magnesium, urea, and creatinine levels. Physical examination of urine of affected animals showed a high degree of turbidity, a large amount of calcium carbonate, and triple phosphate as well as abundant amount of pus cells and red blood cells. The characteristic clinical symptoms of urine retention were observed. Moreover, some animals were found to urinate through an opening in front of the scrotal region.

Dietary magnesium and urolithiasis in growing calves.

The effect of high levels of dietary magnesium (1.4%) alone or in combination with elevated calcium (1.8%) or phosphorus (1.6%) on growth and health of male calves was evaluated during a nine week feeding trial after weaning. Twenty calves were randomly divided into 4 feeding groups consisting of controls, high magnesium, high magnesium and calcium or high magnesium and phosphorus. Elevated dietary minerals caused decreased feed intake and growth rate. Blood urea nitrogen and serum creatinine levels were greatly elevated in calves fed high magnesium or magnesium and phosphorus and serum urea nitrogen was moderately elevated in calves fed high magnesium and calcium. These elevations suggested the occurrence of renal damage as a result of microcrystalline obstruction of renal tubules. Serum magnesium levels were three times normal in calves fed high magnesium or magnesium and phosphorus, but only twice normal in calves fed high magnesium and calcium. High dietary magnesium resulted in a significant depression in blood calcium level. This effect was somewhat overcome by additional dietary calcium Three calves fed the high magnesium diet and two calves fed the high magnesium and phosphorus diet developed urinary tract obstruction. The chemical composition of uroliths recovered from these calves was calcium apatite. Elevated dietary magnesium has been shown to be a cause of urolithiasis in growing male calves. Additional dietary calcium, but not phosphorus, appears to protect calves against urolithiasis induced by elevated dietary magnesium.