Chronic kidney disease screening and renoprotection in type 2 diabetes

Background: Type 2 diabetes (T2D) is a major cause of chronic kidney disease. Control of hypertension and the use of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers especially in those with proteinuria have been shown to protect against chronic kidney disease and delay its progression to kidney failure. Methods: We reviewed the medical records of 169 patients at 12 months with a view of auditing the screening for chronic kidney disease and the use of renoprotective measures. Results: Urinalysis was done in 49.1% and serum creatinine in 50.3%. No patient had glomerular filtration rate estimated. Seventy nine (67.6%) of the hypertensive patients were on anti-hypertensives. ACEI was used in 49 (45.8%) of these patients BP control was optimal in 29.1%. Conclusion: There is poor adherence to guidelines on chronic kidney disease screening and renoprotection in T2D

Biochemical and molecular studies of the polyunsaturated fatty acid desaturation pathway in fish

Fish have an absolute dietary requirement for certain polyunsaturated fatty acids (PUFA) termed “essential fatty acids” (EFA) that include members of both the n-6 and n-3 series typified by linoleic acid, 18:2n-6, and α-linolenic acid, 18:3n-3. However, the biologically active forms of EFA are generally the C20 and C22 metabolites of 18:2n-6 and 18:3n-3, viz. 20:4n-6, 20:5n-3 and 22:6n-3. Some fish species can convert C18 PUFA to the C20 and C22 PUFA through a series of alternating desaturation and chain elongation reactions mediated by microsomal systems containing elongases and Δ6 and Δ5 fatty acid desaturases. In species that cannot perform these conversions, the C20 and C22 PUFA themselves are dietary EFA and their C18 homologues do not satisfy EFA requirements. The extent to which the foregoing statements apply quantitatively to a given fish species varies widely. Therefore, a vital area in lipid nutrition in fish is the provision of sufficient amounts of the correct EFA to satisfy the requirements for normal growth and development, requirements that can vary quantitatively during the life of the fish and are particularly important factors in larval marine fish. This paper reviews the work on defining and characterising the fatty acid desaturation and elongation pathway in fish. Biochemical studies have been advanced by the use of cell cultures which have elucidated key parts of the pathway. Thus, the presence of the so-called Sprecher shunt, where 22:6n-3 is produced from 20:5n-3 through two successive elongations and a Δ6 desaturase followed by peroxisomal chain shortening, was demonstrated in trout. Similarly, the block in the pathway in marine and/or piscivorous fish could be due to either a deficiency of C18-20 elongase or Δ5 desaturase and this varies between different marine species. Recent work has focussed on the molecular biology of the pathway with the cloning of fatty acid desaturases and elongases from a variety of fish species. Zebrafish have been used as a model species and a unique desaturase possessing both Δ6 and Δ5 activity along with an elongase with very high C18-20 activity have been cloned and characterised. Understanding this pathway is of increased importance due to the current dependence of salmonid and marine fish aquaculture on fish oil, the supply of which is becoming increasingly limited and unsustainable, necessitating the use in fish feeds of sustainable plant oils, rich in C18 PUFA, but devoid of C20 and C22 PUFA

Zebrafish cDNA encoding multifunctional fatty acid elongase involved in production of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids

Enzymes that increase the chain length of fatty acids are essential for biosynthesis of highly unsaturated fatty acids. The gLELO gene encodes a protein involved in the elongation of polyunsaturated fatty acids in the fungus Mortierella alpina. A search of the Genbank database identified several EST sequences, including one obtained from zebrafish (Danio rerio), with high similarity to gLELO. The full-length transcript, ZfELO, encoding a polypeptide of 291 amino acid residues was isolated from zebrafish liver cDNA. The predicted amino acid sequence of the open reading frame (ORF) shared high similarity with the elongases of C. elegans and human. When expressed in Saccharomyces cerevisiae, the zebrafish ORF conferred the ability to lengthen the chain of a range of C18, C20 and C22 polyunsaturated fatty acids, indicating that biosynthesis of 22:6n-3 from 18:3n-3 via a 24-carbon intermediate is not only feasible, but that one elongase enzyme can perform all three elongation steps required. The zebrafish enzyme was also able to elongate monounsaturated and saturated fatty acids, and thus demonstrates a greater level of promiscuity in terms of substrate use than any elongase enzyme described previously

Chronic Kidney Disease Screening and Renoprotection in Type 2 Diabetes

Background: Type 2 diabetes (T2D) is a major cause of chronic kidney disease. Control of hypertension and the use of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers especially in those with proteinuria have been shown to protect against chronic kidney disease and delay its progression to kidney failure. Methods: We reviewed the medical records of 169 patients at 12 months with a view of auditing the screening for chronic kidney disease and the use of renoprotective measures. Results: Urinalysis was done in 49.1% and serum creatinine in 50.3%. No patient had glomerular filtration rate estimated. Seventy nine (67.6%) of the hypertensive patients were on anti-hypertensives. ACEI was used in 49 (45.8%) of these patients BP control was optimal in 29.1%. Conclusion: There is poor adherence to guidelines on chronic kidney disease screening and renoprotection in T2D.Fond: Le type 2 le diab\ue8te (T2D) est une cause importante de la maladie chronique de rein. La commande de l'hypertension et l'utilisation des inhibiteurs d'enzyme convertissants d'angiotensine (ACEI) et/ou des dresseurs de r\ue9cepteur de l'angiotensine II particuli\ue8rement dans ceux avec le proteinuria ont \ue9t\ue9 montr\ue9es pour se prot\ue9ger contre la maladie chronique de rein et pour retarder sa progression \ue0 l'\ue9chec de rein. M\ue9thodes: Nous avons pass\ue9 en revue les disques m\ue9dicaux de 169 patients \ue0 12 mois avec une vue d'auditer le criblage pour la maladie chronique de rein et l'utilisation des mesures renoprotective. R\ue9sultats: L'analyse d'urine a \ue9t\ue9 faite en 49.1% et cr\ue9atinine de s\ue9rum dans 50.3%. Aucun patient n'a fait estimer le taux de filtrage glom\ue9rulaire. Soixante-dix-neuf (67.6%) des patients hypertendus \ue9taient sur des antihypertensifs. ACEI a \ue9t\ue9 employ\ue9 dans 49 (45.8%) de ces patients que la commande de BP \ue9tait optimale dans 29.1%. Conclusion: Il y a d'adh\ue9rence pauvre aux directives sur le criblage et le renoprotection chroniques de la maladie de rein dans T2D

Nutritional regulation of hepatocyte fatty acid desaturation and polyunsaturated fatty acid composition in zebrafish (Danio rerio) and tilapia (Oreochromis niloticus)

The desaturation and elongation of [1-14C]18:3n-3 was investigated in hepatocytes of the tropical warm freshwater species, zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus). The hepatocyte fatty acid desaturation/elongation pathway was assayed before and after the fish were fed two experimental diets, a control diet containing fish oil (FO) and a diet containing vegetable oil (VO; a blend of olive, linseed and high oleic acid sunflower oils) for 10 weeks. The VO diet was formulated to provide 1% each of 18:2n-6 and 18:3n-3, and so satisfy the possible EFA requirements of zebrafish and tilapia. At the end of the dietary trial, the lipid and fatty acid composition was determined in whole zebrafish, and liver, white muscle and brain of tilapia. Both zebrafish and tilapia expressed a hepatocyte fatty acid desaturation/elongation pattern consistent with them being freshwater and planktonivorous fish. The data also showed that hepatic fatty acid desaturation/elongation was nutritionally regulated with the activities being higher in fish fed the VO diet compared to fish fed the FO diet. In zebrafish, the main effect of the VO diet was increased fatty acid Δ6 desaturase activity resulting in the production of significantly more 18:4n-3 compared to fish fed the FO diet. In tilapia, all activities in the pathway were greater in fish fed the VO diet resulting in increased amounts of all fatty acids in the pathway, but primarily eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). However, the fatty acid compositional data indicated that despite increased activity, desaturation of 18:3n-3 was insufficient to maintain tissue proportions of EPA and DHA in fish fed the VO diet at the same level as in fish fed the FO diet. Practically, these results indicate that manipulation of tilapia diets in commercial culture in response to the declining global fish oil market would have important consequences for fish fatty acid composition and the health of consumers. Scientifically, zebrafish and tilapia, both the subject of active genome mapping projects, could be useful models for studies of lipid and fatty acid metabolism at a molecular biological and genetic level

Genetic diversity of Mycobacterium tuberculosis Complex in Jos, Nigeria

<p>Abstract</p> <p>Background</p> <p>Nigeria has a high tuberculosis incidence, and genotyping studies of <it>Mycobacterium tuberculosis </it>Complex (MTC) in the country are necessary in order to improve our understanding of the epidemic.</p> <p>Methods</p> <p>Isolates of MTC were isolated from cases of pulmonary tuberculosis in Jos, North Central region of Nigeria during 2006-2008. Drug susceptibility test (DST) was performed on 77 of 111 isolates by proportion method on Lowenstein Jensen (LJ) slope while genotyping of mycobacterial DNA was performed by spoligotyping. The SpolDB4 database and the model-based program 'spotclust' were used to assign isolates to families, subfamilies and variants.</p> <p>Results</p> <p>A total of 111 pulmonary isolates from consecutive tuberculosis patients in the city of Jos, Plateau State, Nigeria were spoligotyped. A total of 84 (76%) of the isolates belonged to the Latin American Mediterranean (LAM) family. Of these, 78 isolates were assigned to the LAM10 lineage. Among these, 66 exhibited identical spoligopatterns. Drug susceptibility profiles obtained were not consistently associated with any spoligopattern.</p> <p>Conclusions</p> <p>The dominance of few <it>M. tuberculosis </it>lineages suggests either a high rate of transmission, frequent import of closely related strains, or a highly conserved genotype. It remains to be confirmed whether the predominance of identical LAM10 represent an outbreak.</p> <p>Spoligotyping was useful to gain an overall understanding of the local TB epidemic. This study demonstrated that the incidence of TB in Jos, Nigeria may be caused by a few successful <it>M. tuberculosis </it>families, dominated by the LAM10 family.</p

Molecular cloning and functional characterization of fatty acyl desaturase and elongase cDNAs involved in the production of eicosapentaenoic and docosahexanoic acids from alpha-linolenic acid in Atlantic salmon (Salmo salar)

Fish are the only major dietary source for humans of omega-3 highly unsaturated fatty acids (HUFA) and, with declining fisheries, farmed fish such as Atlantic salmon (Salmo salar) constitute an increasing proportion of the fish in the human diet. However, the current high use of fish oils, derived from wild capture marine fisheries, in aquaculture feeds is not sustainable in the longer term, and will constrain continuing growth of aquaculture activities. A greater understanding of how fish metabolise and biosynthesise HUFA may lead to effective use of more sustainable aquaculture diets. The study described here contributes to an effort to determine the molecular genetics of the HUFA biosynthetic pathway in salmon, with the overall aim being to determine mechanisms for optimising the use of vegetable oils in Atlantic salmon culture. In this paper we describe the cloning and functional characterisation of two genes from salmon involved in the biosynthesis of HUFA. A salmon desaturase cDNA, SalDes, was isolated that included an open reading frame (ORF) of 1362 bp specifying a protein of 454 amino acids. The protein sequence included all the characteristic features of microsomal fatty acid desaturases, including three histidine boxes, two transmembrane regions, and an N-terminal cytochrome b5 domain containing a haem-binding motif similar to that of other fatty acid desaturases. Functional expression in the yeast, Saccharomyces cerevisiae, showed SalDes is predominantly an omega-3 Δ5 desaturase, a key enzyme in the synthesis of eicosapentaenoic acid (20:5n-3) from α-linolenic acid (18:3n-3). The desaturase showed only low levels of Δ6 activity towards C18 polyunsaturated fatty acids. In addition, a fatty acid elongase cDNA, SalElo, was isolated that includes an ORF of 888 bp, specifying a protein of 295 amino acids. The protein sequence of SalElo includes characteristic features of microsomal fatty acid elongases, including a histidine box and a transmembrane region. Upon expression in yeast, SalElo showed broad substrate specificity for polyunsaturated fatty acids with a range of chain lengths, with the rank order being C18 > C20 > C22. Thus, all fatty acid elongase activities required for the biosynthesis of docosahexaenoic acid (22:6n-3) from 18:3n-3 are displayed by this one polypeptide product

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 mu g, for prevention of PPH during active management of labor. Methods and Findings: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 mu g of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. Conclusions: Misoprostol 600 mu g is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol

Farmers’ knowledge on forage production in smallholder dairy systems of Uganda

The aim of the study was to assess dairy farmers’ knowledge on forage production and utilization in the Lake Victoria crescent and Eastern Highlands Agro Ecological Zones (AEZs) of Uganda. Semi-structured questionnaires were administered to a total of 208 small holder dairy farmers in Masaka (100) and Mbale (108) districts. Data was analyzed using Statistical Package for Social Scientists. While the main source of forage is on farm (67.2%), forage growing is not taken as a tradition among small holder dairy farmers. The most prominent forage species used for feeding livestock are Pennisetum purpureum, Calliandra calothyrsus, Musa paradisiacal (peelings and stems), and Leucaena leucocephala. Milk production increases during months of forage abundance (March to May and September to November) and the observed trends are generally comparable to the seasonal rainfall patterns in Uganda. Forage production among dairy farmers is significantly (P < 0.05) influenced by location, household size, land ownership, forage source and livestock feeding system. Apart from chopping before feeding the animals, minimal processing is done to forage. The study provides a basis for designing interventions for improving fodder production and utilization among Uganda’s smallholder dairy farmers.Buyinza Joel, Sekatuba Jude, Ongodia Gerald, Eryau Kenneth, Nansereko Susan, Opolot Ibwala Vincent, Kwaga Phiona, Akellem Richard, Mudondo Scovia and Agaba Hillar

Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure.

Vδ2+ γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+ T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+ counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminished in vivo expansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequent Pf infection, but also with an increased odds of symptoms once infected. Vδ2+ T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria