Transferrin Variants Research Articles

Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells.

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy.

Abstract 13338: Intravenous Iron for Patients With Iron Deficiency and Acute or Chronic Heart Failure, a Meta Analysis

Iron deficiency is very common in heart failure (HF), both with preserved and reduced ejection fraction (HFp/rEF); and has significant impact on both symptoms and prognosis. This review highlights the effect of use of intravenous iron (IVI) therapy in patients with HFrEF Several databases were searched to identify RCTs that investigate the efficacy and safety of IVI therapy in patients with acute or chronic HF. A meta-analysis was performed using RevMan using random effect model. We used the odds ratio (OR) and mean difference (MD) for dichotomous and continuous outcomes, respectively presented with the corresponding 95% confidence interval (CI). A total of 18 studies were included with 3,436 patients with mean age of 68 years old. There was no statistically significant difference between IVI and placebo in terms of cardiovascular death or all-cause hospital admission. However, IVI was associated with statistically significant lower risk for hospitalization for any cardiovascular disorder and all cause death with OR 0.42 [95% CI 0.28, 0.64, p<0.0001] and 0.61 [95% CI 0.39, 0.96, p=0.03], respectively. Additionally, there was statistically significant variation in serum ferritin and serum transferrin from baseline favoring intravenous iron with MD -189.62 [95%CI -236.55, -142.69, p=0.01], and -7.65 [95% CI -13.43, -1.87, p=0.009], respectively. Furthermore, IVI was associated with a significant improvement in HF patients’ functional status, evaluated by both Kansas City Cardiomyopathy Questionnaire (KCCQ), and changes from baseline in left ventricular ejection fraction (LVEF) with MD -7.14 [95% CI -10.52, -3.76, p<0.0001], and 3.76 [95% CI 2.32, 5.21, p<0.00001], respectively. Our meta-analysis demonstrated the capability of IVI to improve clinically meaningful outcomes as HF-related cardiovascular-related hospitalization as well as functional status; however, intravenous iron showed no difference in term of mortality.

Proteomic map of the differentially expressed proteins in the skin of Ctenopharyngodon idella against Aeromonas hydrophila infection

The skin mucus of fish is an important part of the innate immune system, which is poorly understood at the proteomic level. The study established a complete map of the proteins in the skin mucus of Ctenopharangdon idella (C. idella) and discussed the Differentially Expressed Proteins (DEPs) after Aeromonas hydrophila (A. hydrophila) infection. Using Label Free Liquid Chromatography-Mass Spectrometry (LC–MS/MS) analysis, a total of 126 proteins were identified as differentially expressed, 89 proteins of which were upregulated, and 37 proteins were downregulated. Functional annotations of DEPs showed that the upregulated proteins in the skin mucus of the treated group were mostly associated with complement system and cytoskeleton proteins, whereas downregulated proteins were associated with metabolism. The key upregulated immune proteins were transferrin variant C, lysozyme g, annexin A11, 26S proteasome non-ATPase regulatory subunit 8, hypothetical protein ROHU_000884, 60S ribosomal L7a, calpain-2 catalytic subunit-like protein, calpain-9-like protein, complement component C9, complement C3, cathepsin S, cathepsin Z, 14 kDa apolipo, heat shock protein and intelectin, whereas, leukocyte elastase inhibitor, annexin A11, C-factor-like protein, biotinidase isoform X1 and epidermal growth factor receptor substrate 15-like were the downregulated proteins. Moreover, we for the first-time report proteins such as coactosin, lamin-B2 and kelch 12, which were never reported in fish. Our study directly pointing out the possible immunological biomarkers in the skin mucus of C. idella after A. hydrophila treatment. Each of the protein we report in this study could be used as base to establish their mechanism of action during bacterial infection that may contribute to the strategies against bacterial prevention and control in fishes.

"Hide and seek": Misleading transferrin variants in PMM2-CDG complicate diagnostics.

Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism. Despite the availability of next-generation sequencing techniques and advanced methods for evaluation of glycosylation, CDG screening mainly relies on the analysis of serum transferrin (Tf) by isoelectric focusing, HPLC or capillary electrophoresis. The main pitfall of this screening method is the presence ofTf protein variants within the general population. Althoughreportsdescribe the role of Tf variants leading to falsely abnormal results, their significance in confounding diagnosis in patients with CDG has not been documented so far. Here, we describe two PMM2-CDG cases, in which Tf variants complicated the diagnostic. Glycosylation investigations included classical screening techniques (capillary electrophoresis, isoelectric focusing and HPLC of Tf) and various confirmation techniques (two-dimensional electrophoresis, western blot,N-glycome, UPLC-FLR/QTOF MS with Rapifluor). Tf variants were highlighted following neuraminidase treatment. Sequencing ofPMM2 was performed. In both patients, Tf screening pointed to CDG-II, while second-line analyses pointed to CDG-I. Tf variants were found in both patients, explaining these discrepancies.PMM2causativevariants were identified in both patients. We suggest that a neuraminidase treatment should be performed when a typical CDG Tf pattern is found upon initial screening analysis.

Characterization of human tear proteome reveals differentially abundance proteins in thyroid-associated ophthalmopathy.

BackgroundThyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been systematically studied. The purpose of this study is to compare and analyze the total tear protein profile of TAO patients and to provide protein cues for TAO pathogenesis.MethodsTear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome.ResultsHere, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance.ConclusionIn conclusion, label-free LC-MS/MS is an effective strategy for profiling tear proteins component. Our study provides proteins and pathways altered in TAO and provides protein cues for further study on the precise mechanism of TAO pathogenesis.

Blood protein polymorphism and differentiation of selected indigenous cattle breeds in Nigeria

Genetic variation is the basis of effective improvement in farm animals. Population differentiation is used for objective choice of parental genotypes that constitutes new hybrids in crossbreeding. In Nigeria, population characteristics of selected indigenous cattle breeds have not been fully documented. Therefore, blood protein electrophoretic patterns of selected indigenous cattle breeds in Nigeria were assessed. Blood samples (5mL) were taken underneath the tail by venipuncture from 40 cattle randomly selected from each of the five breeds. The samples were subjected to cellulose acetate electrophoresis to determine the genetic variants of haemoglobin (Hb), carbonic anhydrase (CA) and transferrin (Tf) following standard procedure. Data were analysed using descriptive statistics, cluster analysis and Euclidean genetic distance. Allele frequencies ranged between 0.10 (Hb ) and 0.90 (Hb ), 0.11 (CA ) and 0.89 (CA ) and 0.02 (Tf ) and 0.49 (Tf ) across the breed.Two main clusters from the dendrogram were observed for each of Hb, CA and Tf. Euclidean genetic distance at the blood protein polymorphism level between WF and SG, WF and RB, WF and BK, WF and Muturu were 29, 30, 80 and 93, respectively. Genetic variants of transferring were largest within breed which indicated potential for selection

The many faces of transferrin: Does genotype modulate immune response?

In this study, the expression of pro-inflammatory and iron metabolism genes were analysed under Trypanoplasma borreli (T. borreli) challenge in common carp. Three transferrin (Tf) genotypic groups: two homozygous - DD, GG, and heterozygous DG were intraperitoneally infected with a dose of 2.16 × 105/100 μL parasites. Organ and blood samples were collected at weekly intervals. During the infection period, mortality and parasitaemia were assessed along with measurements of blood iron concentrations and antibody levels. Expression of Tf, Fer, IRP1 and 2, TfR 1a and 1b, Hep, TNF α1 and α2, and IL-1 β was measured in the peak of parasitaemia and the week preceding the peak.Study revealed, that changes in iron blood level induced by parasite were not correlated with the activities of iron homeostasis genes. Neither iron content nor the specific antibody response correlated with survival. We demonstrate that challenged carp, display three distinct, Tf genotype dependent activity patterns of iron homeostasis genes expression. The expected, “classical” way of up-regulation represented homozygous DD individuals. In contrast, GG individuals demonstrated downward trend, while gene expressions of heterozygous DG carp could be defined as an intermediate. We speculate, whether this phenomenon is related to the transferrin molecule itself or to Tf-genotypes being markers of other factors, that influence the iron homeostasis genes activities. We discussed the role of alarmins in triggering the immune response. Distinct genes activating patterns of homozygous genotypes DD and GG had no consequences in terms of mortality rates caused by T.borreli. The highest mortality was observed in the heterozygous group DG.In conclusion, this study suggest that transferrin variant, but not iron blood concentration, has a significant impact on carp immune response to blood parasite infection. This research sheds a new light on the inflammation process and interaction between a host and invaders.

The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n=37), followed by the CD variants (n=27), unclear patterns (n=7), BD variants (n=3), CC variants (n=2), misclassification (n=1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n=22, 28.6%), followed by the toxic effects of substances (n=17, 22.1%), and mental and behavioral disorders attributable to alcohol (n=11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n=880, 37.1%), a personal history of suicide attempts (n=634, 26.7%), and mental and behavioral disorders due to alcohol (n=336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice.

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis.

Work dealing with the monitoring of transferrin isoforms in human serum and other body fluids by capillary electrophoresis is reviewed. It comprises capillary zone electrophoresis and capillary isoelectric focusing efforts that led to the exploration and use of assays for the determination of carbohydrate-deficient transferrin as a marker for excessive alcohol intake, genetic variants of transferrin, congenital disorders of glycosylation and β-2-transferrin, which is a marker for cerebrospinal fluid leakage. This paper provides insight into the development, specifications, strengths, weaknesses, and routine use of the currently known capillary electrophoresis based assays suitable to detect transferrin isoforms in body fluids. The achievements reached so far indicate that capillary zone electrophoresis is an attractive technology to monitor the molecular forms of transferrin in biological specimens as the assays do not require an elaborate sample pretreatment and thus can be fully automated for high-throughput analyses on multicapillary instruments. Assays based on capillary isoelectric focusing are less attractive. They require immunoextraction of transferrin from the biological matrix and mobilization after focusing if instrumentation with a whole-column imaging detector is not available. Interactions of the carrier ampholytes with the iron of transferrin may prevent iron saturation and thus provide more complicated isoform patterns.

Analysis of genetic variants of transferrin in human serum after desialylation by capillary zone electrophoresis and capillary isoelectric focusing.

Capillary electrophoresis analysis of transferrin in human serum is used to assess genetic variants after desialylation with neuraminidase and iron saturation to reduce the complexity of the transferrin pattern and thus facilitate the recognition of transferrin polymorphisms. Asialo-transferrin forms are analyzed by capillary zone electrophoresis using assay conditions as for the monitoring of carbohydrate-deficient transferrin or by capillary isoelectric focusing in a pH 5-8 gradient which requires immunoextraction of transferrin prior to analysis. With the carrier ampholytes used, peaks for iron saturated and iron depleted transferrin are monitored which indicates complexation of iron ions by carrier ampholytes. For BC, CD, and BD genetic variants, the expected peaks for B, C, and D forms of transferrin were detected with both methods. Monitoring of CC patterns revealed three cases, namely those producing double peaks in both methods, a double peak in capillary isoelectric focusing only and a double peak in capillary zone electrophoresis only. For all samples analyzed, data obtained by capillary isoelectric focusing could be confirmed with gel isoelectric focusing. The two capillary electrophoresis methods are shown to represent effective tools to assess unusual transferrin patterns, including genetic variants with dissimilar abundances of the two forms.

Morphological and genetic variability in small island populations of the striped field mouse Apodemus agrarius Pallas, 1771

Morphological (craniometrical characteristics and variations of cusp t3 on the second upper molar (M2)) and genetic (polymorphism of chromosomes and blood proteins) variability was analyzed in small island populations of the striped field mouse Apodemus agrarius Pallas, 1771 from the Peter the Great Bay (Sea of Japan). It was found that the absence of t3 on M2 is not a specific trait for A. agrarius. It was demonstrated that the population of field mice on the Bolshoy Pelis Island significantly differs from the populations from other islands and from the mainland according to the craniometrical parameters, teeth phenes, and variants of blood transferrin. The possible age of establishment of the island populations of the striped field mouse is discussed.

Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation.

Transferrin, a major glycoprotein has different isoforms depending on the number of sialic acid residues present on its oligosaccharide chain. Genetic variants of transferrin as well as the primary (CDG) & secondary glycosylation defects lead to an altered transferrin pattern. Isoform analysis methods are based on charge/mass variations. We aimed to compare the performance of commercially available capillary electrophoresis CDT kit for diagnosing congenital disorders of glycosylation with our in-house optimized HPLC method for transferrin isoform analysis. The isoform pattern of 30 healthy controls & 50 CDG-suspected patients was determined by CE using a Carbohydrate-Deficient Transferrin kit. The results were compared with in-house HPLC-based assay for transferrin isoforms. Transferrin isoform pattern for healthy individuals showed a predominant tetrasialo transferrin fraction followed by pentasialo, trisialo, and disialotransferrin. Two of 50 CDG-suspected patients showed the presence of asialylated isoforms. The results were comparable with isoform pattern obtained by HPLC. The commercial controls showed a <20% CV for each isoform. Bland Altman plot showed the difference plot to be within +1.96 with no systemic bias in the test results by HPLC & CE. The CE method is rapid, reproducible and comparable with HPLC and can be used for screening Glycosylation defects.

A transferrin variant as the targeting ligand for polymeric nanoparticles incorporated in 3-D PLGA porous scaffolds

We have developed doxorubicin (DOX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (DP) conjugated with polyethylene glycol (PEG) and transferrin (Tf) to form Tf-PEG-DPs (TPDPs), and incorporated these TPDPs into three-dimensional (3-D) PLGA porous scaffolds to form a controlled delivery system. To our knowledge, this represents the first use of a Tf variant (oxalate Tf) to improve the targeted delivery of drug-encapsulated nanoparticles (NPs) in PLGA scaffolds to PC3 prostate cancer cells. The PLGA scaffolds with TPDPs incorporated have been shown to release drugs for sustained delivery and provided a continuous release of DOX. The MTS assay was also performed to determine the potency of native and oxalate TPDPs, and a 3.0-fold decrease in IC50 values were observed between the native and oxalate TPDPs. The lower IC50 value for the oxalate version signifies greater potency compared to the native version, since a lower concentration of drug was required to achieve the same therapeutic effect. These results suggest that this technology has potential to become a new implantable polymeric device to improve the controlled and targeted drug delivery of Tf-conjugated NPs for cancer therapy.

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably β-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.

It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test.

Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism. A blood sample from a patient with suspected alcohol abuse was analyzed with HPLC, isoelectric focusing, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), immunoprecipitation and SDS-Page. Sanger sequencing of Tf was performed to detect Tf mutations. HPLC, SDS-Page and IEF showed a distinctly increased disialo-Tf fraction while the tetrasialo-Tf fraction was decreased, ESI-TOF-MS confirmed these results. Sanger sequencing revealed the Tf mutation c.1889 A>C, deleting a Tf glycosylations site and thereby causing elevated disialo-Tf levels. Transferrin mutations can severely impair the diagnostics of chronic alcohol abuse by causing false positive results. This has to be considered when CDT screening is used to detect alcoholism.

Transferrin variants: Pitfalls in the diagnostics of Congenital disorders of glycosylation

ObjectivesTransferrin variants can hinder the diagnostic process in cases of suspected Congenital disorders of glycosylation which affect N-Glycosylation. In addition they can impair the use of Carbohydrate deficient Transferrin as a biomarker for chronic alcohol abuse, in which Asialo-Transferrin and Disialo-Transferrin are increased. We present a novel transferrin variant as well as an overview of transferrin mutations found at our laboratory. Design and methodsBlood samples from patients with suspected CDG were analyzed using the standard diagnostic procedures of Isoelectric focusing and High-performance liquid chromatography as well as the additional procedures of neuraminidase digestion of glycans and Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS). ResultsFour known and one previously unreported transferrin variants were identified. Neuraminidase digestion and ESI-TOF MS revealed changes in charge of the transferrin molecules while the glycosylation status was found to be normal. ConclusionTransferrin variants are pitfalls in the diagnostics of CDG. The found variants change the charge of the transferrin molecule, thus affecting the standard diagnostic procedures. Neuraminidase digestion as well as ESI-TOF MS can identify variants and mutations in a laboratory context.

The novel transferrin E592A variant impairs the diagnostics of congenital disorders of glycosylation

BackgroundThe analysis of serum transferrin either by high-performance liquid chromatography (HPLC) or isoelectric focusing (IEF) is the standard diagnostic procedure in patients with the suspicion of a congenital disorder of glycosylation (CDG). Carbohydrate-deficient transferrin (CDT) is also analysed in monitoring programmes in cases of alcohol abuse. We report a novel transferrin variant that impairs the analysis using conventional methods and propose alternative forms of analysis. MethodsTransferrin samples were analysed using HPLC, immunoprecipitation followed by SDS-PAGE and IEF. Neuraminidase treatment followed by conventional IEF and electrospray ionization time of flight mass spectrometry (ESI-TOF MS) were applied before sequencing of the transferrin gene was performed. ResultsThe novel transferrin variant E592A, found both in homozygous and heterozygous form, causes an altered charge of the transferrin molecule, which changes the results of IEF and HPLC and mimics an increase in trisialo-transferrin. The change in charge can be detected either by neuraminidase digestion followed by IEF or by ESI-TOF MS. ConclusionConventional diagnostic methods for CDG are hindered by the novel transferrin E592A. Neuraminidase treatment followed by IEF and ESI-TOF MS can identify the mutation. The mutation appears to be functionally normal.

Determination of carbohydrate-deficient transferrin in a Han Chinese population

BackgroundCarbohydrate-deficient transferrin (CDT) is a widely used alcohol biomarker. Because of the high prevalence of chronic alcohol abuse in many countries, CDT plays an important role in the areas of traffic, clinical, and forensic medicine. However, CDT levels have not been determined in the Han Chinese population. Therefore, we investigated the frequency of genetic transferrin variants and the relationship between CDT levels and alcohol consumption in this population. From this data, we established a CDT cut-off for Han Chinese and evaluated the analytical performance of the CDT capillary zone electrophoresis system.ResultsThe prevalence of transferrin variants was 4.14%. The mean CDT level of the reference group was 0.73%. We recommended CDT level >1.5% as cut off standard of alcohol intake to ensuring the specificity was best. The CDT test total precision for 0.5%, 0.7%, and 1.55% was 14.4%, 11.5%, and 7.2%, respectively. The data showed good linearity in the studied range of 0.6% to 8.2%.ConclusionsThese results demonstrate that CDT is a useful marker to detect heavy daily alcohol consumption. We proposed and evaluated the first CDT cut-off for the Han Chinese population, and we showed that the CDT capillary zone electrophoresis system is a reliable analytic method.

Improving the systemic drug delivery efficacy of nanoparticles using a transferrin variant for targeting

Targeted therapy for the treatment of cancers using nanoparticles (NPs) decorated with transferrin (Tf) has been relatively successful, as several such nanocarriers are currently undergoing clinical trials. However, since native Tf has a low probability of delivering its payload due to its short residence time in the cell, or low cellular association, there is room to significantly improve the potency of current systems. We pioneered the redesign of this targeting ligand by altering the ligand–metal interaction, as suggested by our mathematical model, and here we present the first study to investigate the enhanced therapeutic efficacy of NPs conjugated to our engineered oxalate Tf. Our mathematical model was first used to predict that NPs conjugated to oxalate Tf will exhibit a higher degree of cellular association compared to native Tf-conjugated NPs. Our in vitro trafficking experiments validated the model prediction, and subsequent in vitro and in vivo efficacy studies demonstrated that this increase in cellular association further translates into an enhanced ability to deliver chemotherapeutics. Our findings signify the importance of the cellular trafficking properties of targeting ligands, as they may significantly influence therapeutic potency when such ligands are conjugated to NPs. Given the early success of a number of native Tf-conjugated NPs in clinical trials, there is potential for using Tf-variant based therapeutics in systemic drug delivery applications for cancer treatment.

Effects of Malaria on Iron Stores in the Pregnant Women of Buea and Tiko Health District, South West Region, Cameroon

Malaria infection has a complex effect on iron metabolism that may affect the interpretation of haemoglobin, serum ferritin, serum transferrin and serum iron. The main objective of this study was to determine the effect of malaria parasitaemia on the iron store forms of pregnant women in the Buea and Tiko health districts of the S.W Region of Cameroon. This investigation was carried out from the 3rd of August 2011 to the 30th of April 2012. The non-probabilistic sampling method was used to recruit a total of 377 pregnant women into the study. Questionnaires were used for the collection of secondary data. The microscopy method was used to detect the presence of malaria infection. A total of 41.4% (156/377) of the pregnant women were infected with Plasmodium falciparum. Of the infected cases; 32.1% had low levels of serum ferritin ( 360 mg/dl), and 45.5% had low levels of serum iron (<9.0 μmol/l). The quantitative results using regression analysis justified that 88% variation in serum ferritin, transferrin and iron were accounted for by variation in malaria parasitaemia during the second and the third trimesters. Serum iron, ferritin and transferrin measurements should be incorporated as one of the routine laboratory tests during the regular antenatal care visits.