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The reaction of the vanadyl ion (VO 2+ ) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid-base titrations. The species distribution diagrams for the high-molecular-mass (HMM) proteins with oxidovanadium(IV) under physiological pH were dominated by VO(HMM) 2 , VOL(HMM) for unsubstituted ligands (L - = Im4COO - and Im2COO - ). However, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH were dominated by VOL 2 , VO(HMM) 2 and VO 2 L 2 (HMM). These species were further confirmed by LC-MS, MALDI-TOF-MS and EPR studies. The glucose-stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at a 1 µM concentration, which was established through cytotoxicity studies via the MTT assay. The neutral complexes, especially VO(MeIm2COO) 2 , showed promising results in the stimulation of insulin secretion than the cationic [VO(MeIm2CH 2 OH) 2 ] 2+ complex and the vanadium salt. Oxidovanadium(IV) complexes reduced insulin stimulation significantly under normoglycaemic levels but showed positive effects on insulin secretion under hyperglycaemic conditions (33.3 mM glucose media). The islets exposed to oxidovanadium(IV) complexes under hyperglycaemic conditions displayed a significant increase in the stimulatory index with 1.19, 1.75, 1.53, 1.85, 2.20 and 1.29 observed for the positive control (sulfonylurea:gliclazide), VOSO 4 , VO(Im4COO) 2 , VO(Im2COO) 2 , VO(MeIm2COO) 2 and VO(MeIm2CH 2 OH) 2 2+ , respectively. This observation showed a potential further effect of vanadium complexes towards type 2 diabetes and has been demonstrated for the first time in this study.

With rising demand for food and the threats posed by climate change, The Gambia faces significant challenges in ensuring sufficient and nutritious food for its population. To address these challenges, there is a need to increase domestic food production while limiting deforestation and land degradation. In this study, we modified the FABLE Calculator, a food and land-use system model, to focus on The Gambia to simulate scenarios for future food demand and increasing domestic food production. We considered the impacts of climate change on crops, the adoption of climate change adaptation techniques, as well as the potential of enhanced fertiliser use and irrigation to boost crop productivity, and assessed whether these measures would be sufficient to meet the projected increase in food demand. Our results indicate that domestic food production on existing cropland will not be sufficient to meet national food demand by 2050, leading to a significant supply-demand gap. However, investments in fertiliser availability and the development of sustainable irrigation infrastructure, coupled with climate change adaptation strategies like the adoption of climate-resilient crop varieties and optimised planting dates, could halve this gap. Addressing the remaining gap will require additional strategies, such as increasing imports, expanding cropland, or prioritising the production of domestic food crops over export crops. Given the critical role imports play in The Gambia's food supply, it is essential to ensure a robust flow of food imports by diversifying partners and addressing regional trade barriers. Our study highlights the urgent need for sustained investment and policy support to enhance domestic food production and food imports to secure sufficient and healthy food supplies amidst growing demand and climate change challenges., Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-024-01444-1., Competing Interests: Conflict of interestThe authors do not have any competing interests to declare., (© The Author(s) 2024.)

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) proteins, we demonstrated that R-DOTAP nanoparticles promoted strong cellular- and antibody-mediated immune responses in both monovalent and bivalent vaccines. R-DOTAP-based vaccines induced antigen-specific and polyfunctional CD8 + and CD4 + effector T cells and memory T cells, respectively. Antibody responses induced by R-DOTAP showed a balanced Th1/Th2 type immunity, neutralizing activity and protection of mice from challenge with live SARS-CoV2 or influenza viruses. R-DOTAP also facilitated significant dose sparing of the vaccine antigens. These studies demonstrate that R-DOTAP is an excellent immune stimulator for the production of next-generation subunit vaccines containing multiple recombinant proteins.

Certain types of cationic lipids have shown promise in cancer immunotherapy, but their mechanism of action is poorly understood. In this study, we describe the properties of an immunotherapeutic consisting of the pure cationic lipid enantiomer R-1,2-dioleoyl-3-trimethyl-ammonium-propane (R-DOTAP) formulated with modified viral or self-peptide Ags. R-DOTAP formulations with peptide Ags stimulate strong cross-presentation and potent CD8 T cell responses associated with a high frequency of polyfunctional CD8 T cells. In a human papillomavirus tumor model system, a single s.c. injection of tumor-bearing mice with R-DOTAP plus human papillomavirus Ags induces complete regression of large tumors associated with an influx of Ag-specific CD8 T cells and a reduction of the ratio of regulatory/Ag-specific CD8 T cells. R-DOTAP also synergizes with an anti-PD1 checkpoint inhibitor, resulting in a significant inhibition of B16 melanoma tumor growth. We found that R-DOTAP stimulates type I IFN production by dendritic cells in vivo and in vitro. s.c. injection of R-DOTAP results in an IFN-dependent increase in draining lymph node size and a concomitant increase in CD69 expression. Using knockout mice, we show that type I IFN is required for the induction of CD8 T cell activity following administration of R-DOTAP plus Ag. This response requires Myd88 but not TRIF or STING. We also show that R-DOTAP stimulates both TLR7 and 9. Collectively, these studies reveal that R-DOTAP stimulates endosomal TLRs, resulting in a Myd88-dependent production of type I IFN. When administered with Ag, this results in potent Ag-specific CD8 T cell responses and antitumor activity., (Copyright © 2019 by The American Association of Immunologists, Inc.)

The purpose of antithrombotic therapy is the prevention of thrombus formation and/or its extension with a minimum risk of bleeding. The inhibition of a variety of proteolytic processes, particularly those of the coagulation cascade, has been reported as a property of plant protease inhibitors. The role of trypsin inhibitors (TIs) from Delonix regia (Dr) and Acacia schweinfurthii (As), members of the Kunitz family of protease inhibitors, was investigated on blood coagulation, platelet aggregation, and thrombus formation. Different from Acacia schweinfurthii trypsin inhibitor (AsTI), Delonix regia trypsin inhibitor (DrTI) is a potent inhibitor of FXIa with a K iapp of 1.3 × 10 -9  M. In vitro, both inhibitors at 100 µg corresponding to the concentrations of 21 μM and 15.4 μM of DrTI and AsTI, respectively, increased approximately 2.0 times the activated partial thromboplastin time (aPTT) in human plasma compared to the control, likely due to the inhibition of human plasma kallikrein (huPK) or activated factor XI (FXIa), in the case of DrTI. Investigating in vivo models of arterial thrombus formation and bleeding time, DrTI and AsTI, 1.3 µM and 0.96 µM, respectively, prolonged approximately 50% the time for total carotid artery occlusion in mice compared to the control. In contrast to heparin, the bleeding time in mice treated with the two inhibitors did not differ from that of the control group. DrTI and AsTI inhibited 49.3% and 63.8%, respectively, ex vivo murine platelet aggregation induced by adenosine diphosphate (ADP), indicating that these protein inhibitors prevent arterial thrombus formation possibly by interfering with the plasma kallikrein (PK) proteolytic action on the intrinsic coagulation pathway and its ability to enhance the platelet aggregation activity on the intravascular compartment leading to the improvement of a thrombus.

Background: Although hematological indices cannot in entirety be used to diagnose diseases or defects, the appropriate interpretation of these indices could complement diagnostics such as microscopy and serology for numerous illnesses in children. This study sought to evaluate distinct hematological indices characterizing different childhood illnesses., Methods: Full blood counts from 150 children (age range from 1 to 15 year) presenting different disease conditions at the Tamale Central Hospital were assessed. The hematological indices were compared between disease categories, and relationships between disease indicators were determined., Results: The prevalence of the diagnosed childhood illness were: 50.7% malaria, 20.0% diarrhea, 13.3% typhoid fever, 10.0% Sickle Cell Disease (SCD), and 6.0% malaria-typhoid co-infection. Fever was diagnosed in a majority (66.0%) of the children, but was independent of each disease group, (χ 2  = 9.18, P = .057). Of the 24 hematological indices analyzed, eight; red blood cell (RBC) (P < .001), hemoglobin (Hb) (P < .001), mean cell volume (MCV) (P = .002), mean cell hemoglobin (MCH) (P < .001; lowest and below normal range for SCD), red cell distribution width (RDW&#95;CV) (P < .001), eosinophil percentage [EOS (%)] (P = .001), eosinophil number [EOS#] (P = .002), and platelets (PLT) (P = .001; lowest for malaria) differed significantly across the different disease groups. Levels of Hb and/or MCV were below the normal reference ranges for most of the diagnosed diseases. In addition, low PLT and MCH were respectively distinct for children with malaria and SCD., Conclusion: Hematological indices including Hb, MCV and PLT, or MCH may be useful indices that could incite further diagnostic tests for malaria or SCD among children in Ghana., (© 2018 Wiley Periodicals, Inc.)

Extensive research has found that marriage provides health benefits to individuals, particularly in the U.S. The rise of cohabitation, however, raises questions about whether simply being in an intimate co-residential partnership conveys the same health benefits as marriage. Here, we use OLS regression to compare differences between partnered and unpartnered, and cohabiting and married individuals with respect to self-rated health in mid-life, an understudied part of the lifecourse. We pay particular attention to selection mechanisms arising in childhood and characteristics of the partnership. We compare results in five countries with different social, economic, and policy contexts: the U.S. (NLSY), U.K. (UKHLS), Australia (HILDA), Germany (SOEP), and Norway (GGS). Results show that living with a partner is positively associated with self-rated health in mid-life in all countries, but that controlling for children, prior separation, and current socio-economic status eliminates differences in Germany and Norway. Significant differences between cohabitation and marriage are only evident in the U.S. and the U.K., but controlling for childhood background, union duration, and prior union dissolution eliminates partnership differentials. The findings suggest that cohabitation in the U.S. and U.K., both liberal welfare regimes, seems to be very different than in the other countries. The results challenge the assumption that only marriage is beneficial for health.

Nanostructured lipid carriers (NLCs) of Leonotis leonurus were successfully produced using high-pressure homogenisation (HPH) on a LAB 40 homogeniser. The particle size was determined for the formulation as well as short-term stability study. The formulation was exposed to Chang liver cells for a glucose uptake study and to INS-1 cells for a chronic insulin release study under normoglycaemic and hyperglycaemic conditions. The particle size of the extract NLC was 220 nm with a PdI of 0.08 after homogenisation at 800 bar. The formulation was stable at the tested temperatures. The extract NLC formulation at 1 µg/ml improved glucose uptake, relative to the control liver cells. Insulin release in INS-1 cells was also elevated under hyperglycaemic conditions when exposed to the NLCs, in comparison with the control untreated cells and the non-formulated extract. The plant extract encapsulated in NLC improved the uptake of glucose and enhanced the insulin sensitivity in vitro, compared to the extract.

Despite evidence that first-birth timing influences women's health, the role of marital status in shaping this association has received scant attention. Using multivariate propensity score matching, we analyze data from the National Longitudinal Survey of Youth 1979 to estimate the effect of having a first birth in adolescence (prior to age 20), young adulthood (ages 20-24), or later ages (ages 25-35) on women's midlife self-assessed health. Findings suggest that adolescent childbearing is associated with worse midlife health compared to later births for black women but not for white women. Yet, we find no evidence of health advantages of delaying first births from adolescence to young adulthood for either group. Births in young adulthood are linked to worse health than later births among both black and white women. Our results also indicate that marriage following a nonmarital adolescent or young adult first birth is associated with modestly worse self-assessed health compared to remaining unmarried., (© American Sociological Association 2015.)

One of the many control mechanisms of serine proteinases is their specific inhibition by protein proteinase inhibitors. An extract of Acacia schweinfurthii was screened for potential serine proteinase inhibition. It was successfully purified to homogeneity by precipitating with 80% (v/v) acetone and sequential chromatographic steps, including ion-exchange, affinity purification and reversed-phase high performance liquid chromatography. Reducing sodium dodecyl sulphate polyacrylamide gel electrophoresis conditions revealed an inhibitor (ASTI) consisting of two polypeptide chains A and B of approximate molecular weights of 16 and 10 kDa, respectively, and under non-reducing conditions, 26 kDa was observed. The inhibitor was shown to inhibit bovine trypsin (Ki of 3.45 nM) at an approximate molar ratio of inhibitor:trypsin (1:1). The A- and B-chains revealed complete sequences of 140 and 40 amino acid residues, respectively. Sequence similarity (70%) was reported between ASTI A-chain and ACTI A-chain (Acacia confusa) using ClustalW. The B-chain produced a 76% sequence similarity between ASTI and Leucaena leucocephala trypsin inhibitor.

As nonmarital childbearing becomes a dominant pathway to family formation, understanding its long-term consequences for children's well-being is increasingly important. Analysis of linked mother-child data from the 1979 National Longitudinal Survey of Youth indicates a negative association of having been born to a never-married mother with adolescent self-assessed health but not with depressive symptoms. We also consider the role of mothers' subsequent union histories in shaping the adolescent health outcomes of youth born to unmarried mothers. With two exceptions, unmarried mothers' subsequent unions appear to have little consequence for the health of their offspring during adolescence. Adolescents whose mothers subsequently married and remained with their biological fathers reported better health, yet adolescents whose mothers continuously cohabited with their biological fathers without subsequent marriage reported worse adolescent mental health compared with adolescents whose mothers remained continually unpartnered.

Despite high rates of nonmarital childbearing in the U.S., little is known about the health of women who have nonmarital births. We use data from the NLSY79 to examine differences in age 40 self-assessed health between women who had a premarital birth and those whose first birth occurred within marriage. We then differentiate women with a premarital first birth according to their subsequent union histories and estimate the effect of marrying or cohabiting versus remaining never-married on midlife self-assessed health, paying particular attention to the paternity status of the mother's partner and the stability of marital unions. To partially address selection bias, we employ multivariate propensity score techniques. Results suggest that premarital childbearing is negatively associated with midlife health for white and black (but not Hispanic) women. We find no evidence that these negative health consequences of nonmarital childbearing are mitigated by either marriage or cohabitation for black women. For other women, only enduring marriage to the biological father is associated with better health than remaining unpartnered.

This paper examines the factors associated with the tempo of low-income couples' relationship progression into sexual involvement and coresidence. Data come from a recently-collected survey, the Marital and Relationship Survey (MARS) that obtained information from low- to moderate-income married and cohabiting couples. Over one-fifth of male and female respondents reported becoming sexually involved with their current partner within the first week of dating. Entrance into shared living was also quite rapid; about one-third of respondents moved in with their partner within 6 months. Furthermore, about two-thirds of married respondents initially cohabited with their partners. Indicators of family disadvantage accelerated entrance into sexual involvement and coresidence; these effects are more pronounced for women than men. Our results also suggest that the pace of relationship progression, into sexual involvement as well as shared living, has accelerated among unions formed more recently.

In humans, deficiency of galactose-1-phosphate uridyltransferase (GALT) can lead a metabolic disorder Classic Galactosemia. Although the biochemical abnormalities associated with this disease have been described in detail, few attempts have been made to characterize the pathogenic mechanisms of this disorder at the molecular level. Here we report the use of high-throughput DNA microarray to examine how galactose affects gene expression in isogenic yeast models that are deficient in either galactokinase (GALK) or GALT, two enzymes which are essential for normal galactose metabolism. We confirmed that the growth of our GALT-deficient, but not GALK-deficient yeast strain ceased 4 h after challenge with 0.2% galactose. Such inhibition was not associated with a reduction of ATP content and was reversible after removal of galactose from medium. We compared the gene expression profiles of the GALT-deficient and GALK-deficient cells in the presence/absence of galactose. We revealed that in the absence of galactose challenge, a subset of genes involved in RNA metabolism was expressed at a level 3-fold lower in the GALT-deficient cells. Upon galactose challenge, significantly more genes involved in various aspects of RNA metabolism and almost all ribosomal protein genes were downregulated in the GALT-deficient, but not GALK-deficient cells. Remarkably, genes involved in inositol biosynthesis and turnover were exclusively induced at high level in the galactose-intoxicated GALT-deficient cells. Our data thus suggested that RNA metabolism, ribosome biogenesis, and inositol metabolism were likely targets for galactose-1-phosphate, a toxic intermediate that is uniquely accumulated under GALT-deficiency.

This study was carried out to determine the feasibility of using ultrasonography for goitre estimation in the field situation. It is a cross sectional study that was conducted using community based cluster sample. Thyroid sonography was performed on 112 randomly selected school children aged 10 -15 years from two districts in the Greater Accra area of Ghana, using normative values for thyroid volume recommended by WHO/ICCIDD. The mean age of all subjects was 13.5 years+/-0.13 SEM. The male to female ratio was 1:1. The mean height and weight of the children were 1.5 metres+/-0.9 SEM and 38.1 Kg+/-0.7 SEM, respectively. The mean body surface area was 1.27 m2+/-0.2. There were no significant gender differences in their ages (13.6yrs+/-0.2 SEM, 13.4yrs+/-0.1 SEM, respectively) and height (1.50m+/-1.6 SEM, 1.46m+/-1.7 SEM, respectively). The girls (40.0kg+/-1.2 SEM) weighed more than the boys (35.6kg+/-1.1). The mean and median urinary iodine concentration were 82.4+/-8.5 SEM and 67.9 ug/l, respectively. All the children examined had normal thyroid sonogram. The thyroid volumes ranged from 3.6 ml to 15.3ml. The mean thyroid volume was 7.0ml+/-0.2 SEM and the thyroid volume was higher in the girls (7.5ml+/-0.3 SEM) than the boys (6.5ml+/-0.2 SEM). The criteria of thyroid volume per age and sex yielded a goitre prevalence of 1.8 %. In contrast, the criteria of thyroid volume by surface area yielded a goitre prevalence of 8 %. Our study has shown that it is feasible to employ ultrasonography for field studies to determine goitre prevalence in school children in a developing country such as Ghana. However, the best criteria for goitre in children in Ghana, requires to be confirmed in future studies.

A phase II study of the dolastatin 15 analog LU 103793 was conducted by the North Central Cancer Treatment Group in patients with advanced non-small-cell lung cancer (SCLC). Previously untreated patients received this agent at a dosage of 2.5 mg/m2 as a 5-minute intravenous infusion for 5 consecutive days every 3 weeks. Between September 1997 and July 1998, 17 patients were accrued in this study. Forty-two treatment cycles were administered with relatively modest toxicity. No responses were seen. This agent appears to be inactive in the treatment of advanced non-SCLC.

Staphylokinase variant SY161 is a recombinant mutant of the Staphylococcus aureus polypeptide staphylokinase (Sak), and is currently in human clinical trials as a thrombolytic agent. The 15 kDa single chain SY161 protein is expressed as a soluble cytoplasmic product in E. coli with a single cysteine inserted near the N-terminus. The protein as extracted from E. coli is a mixture of both monomeric and intermolecularly disulfide crosslinked species. To improve protein purification yields SY161 is sulfitolyzed during the early stages of production, preventing disulfide formation. The protein is later modified during manufacturing to incorporate a single 5 kDa polyethylene glycol group on the single sulfhydryl sidechain. We have developed and qualified a reverse-phase chromatographic method to quantitate SY161 during product manufacturing. We discuss the use of the assay during manufacturing development to monitor fermentation yields, the SY161 PEGylation reaction, and as an in-process manufacturing control assay. The assay has been applied as a product purity and identity release assay and is suitable for use in assessing product structural integrity during stability testing. The assay has a linear range of quantitation for SY161 from at least 0.15 to 16 micro g, and is-in addition capable of detecting and quantitating protein de-PEGylation events and host cell-derived protein contaminants., (Copyright 2003 John Wiley & Sons, Ltd.)

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy., Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment., Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P =.73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P =.12)., Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.

The goal of this study was to perform preformulation development of SY161 by using statistical design methods to understand the effects of buffer strength, NaCl concentration, and pH on conformation and stability of the protein. It was also important to elucidate interactions between these factors. A central composite design using a 2-level full-factorial study was performed. Secondary structure was evaluated using circular dichroism. Stability toward unfolding was investigated using high-sensitivity differential scanning calorimetry. Depegylation, aggregation, and protein loss were evaluated using SEC-HPLC with on-line light scattering, at time zero and after a 2-week stability study. Response surface plots clearly show optimal pH, NaCl, and buffer conditions. Interactions between pH and NaCl as well as pH and buffer concentration are observed. Tm is seen to be predictive of SY161 stability. Secondary structure changes were minimal and did not influence stability. Statistical design was very effective in providing an understanding of the effects of the formulation components on SY161 stability.

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.

Objective: To ascertain the severity of IDD in some rural communities in upper east of Ghana and to urge the establishment of intervention and control measures for IDD., Subjects and Study Design: A total of 1061 subjects, made up of about an equal number of children (8-14 years) and women of childbearing age (15-45 years) from seven Sekoti villages and five Builsa villages of the upper east of Ghana were examined for goitre by the palpation method. In addition, every tenth subject examined, provided urine for urinary iodine determination., Results: 68.8% of the subjects had goitre; 9.9% had visible goitre. The goitre rates of the children from Builsa (77.2%) were significantly higher than those from Sekoti (59.1%) [z = 4.5; p < 0.001]. The overall prevalence of goitre and visible goire in women in the two areas were 70.8% and 15.4% respectively. The women of Sekoti had more goitres (76.6%) but less visible goitres (8.8%) than those of Builsa (63.5% and 21.9%) [p < 0.001). The median urinary iodine level for the two survey areas was 1.6 micrograms/dl. 72% of subjects and urinary iodine less 2 micrograms/dl/24% had urinary iodine levels in the range 2-5 micrograms/dl and the remainder had urine iodine in the range 5-10 micrograms/dl., Conclusions: These findings indicate severe IDD in Sekoti and Builsa areas requiring urgent action. Further studies are indicated to determine the cause(s) of the IDD endemia.

Incorporation of ganglioside GM1 into liposomes composed of phosphatidylcholine (PC) and cholesterol significantly increases their blood circulation time. Dipalmitoyl PC (DPPC) and distearoyl PC (DSPC) are the most commonly used saturated phospholipids employed in the preparation of long-circulating liposome formulations. Physical studies were performed on different formulations of these liposomes in an attempt to understand the effects of the matrix lipid chain length and GM1 concentration on the use of these liposomes as long-circulating drug delivery systems. The GM1/PC mixtures existed in different physical states: a lamellar state with components exhibiting miscibility (which is the desired state for drug delivery), a mixed micellar phase, and also a smectic mesophase. GM1 is miscible with DSPC bilayers up to a concentration of 25 mol%, beyond which conversion into the metastable mesophase occurs. By 30 mol%, solubilization into the mixed micellar state occurs. With DPPC, the metastable mesophase occurs at 33-38 mol% of GM1, with mixed micelles being formed at higher concentrations. The addition of cholesterol led to an inhibition of micelle formation. This study also indicates that GM1 stabilizes DPPC bilayers while destabilizing DSPC bilayers. On the basis of the interactions of GM1 with DPPC and DSPC, a new hypothesis for stabilization of PC bilayers is proposed, which also explains the destabilization of PC with C18.0 and higher. The longest circulating GM1 liposome formulations are predicted from this study.

Purpose: The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation., Methods: Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study., Results: Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol-percent of PEG(1,000-3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C(16:0) to C(14:0) caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C(18:0). Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE)., Conclusions: These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.

Purpose: The purpose of this study was to investigate polyethyleneglycol (PEG)-phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid mixtures in an attempt to explain the effect of cholesterol on liposome circulation time., Methods: Differential scanning calorimetry, NMR, electron microscopy, dynamic light scattering and fluorescence spectroscopy were the major methods used., Results: Studies performed in the absence of cholesterol indicated the formation of three distinct physical states depending on the chain length of PEG in PEG-PE. Mixed micelle formation was observed at concentrations of PEG(1,000)-DPPE above 7 mol-% of lipid. Phase separated lamellae were observed at all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710-717 (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into the lipid bilayer, the formation of phase separated lamellae was completely inhibited and the formation of mixed micelles significantly reduced. At high concentrations of PEG(1,000)-PE, solubilization of the bilayer occurred with preferential solubilization of cholesterol over phosphatidylcholine. Maximum steric stabilization (surface protection) was observed with low concentrations of short chain PEG-PE and high concentrations of cholesterol., Conclusions: The study provides a physical mechanism for the following observations: the blood circulation time is significantly increased or decreased with liposomes highly enriched with cholesterol or PEG-PE respectively.