Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness.Conclusions/SignificanceDuring this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.     

A Preformulation Strategy for the Selection of Penetration Enhancers for a Transungual Formulation

Onychomycosis is associated with the cutaneous fungal infection of the nail and the nail folds (skin surrounding the nail). It is therefore important to target drug delivery into the nail folds along with nail plate and the nail bed. Systematic and strategic selection of the penetration enhancers specific for the skin and the nail is discussed. Twelve penetration enhancers were screened for their ability to improve solubility, in vitro nail penetration, in vitro skin permeation, and in vitro skin penetration of the antifungal drug ciclopirox olamine. In contrast to transdermal drug delivery, the main selection criteria for skin penetration enhancer in topical drug delivery were increased drug accumulation in the epidermis and minimal permeation across the skin. Thiourea improved the solubility and nail penetration of ciclopirox olamine. It also showed enhancement in the transungual diffusion of the drug. Propylene glycol showed a 12-fold increase in solubility and 3-fold increase in epidermal accumulation of ciclopirox olamine, while minimizing the transdermal movement of the drug. Thiourea was the selected nail permeation enhancer and propylene glycol was the selected skin penetration enhancer of ciclopirox olamine. A combination of the selected enhancers was also explored for its effect on drug delivery to the nail and nail folds. The enhancer combination reduced the penetration of ciclopirox in the skin and also the permeation through the nail. The proposed preformulation strategy helps to select appropriate enhancers for optimum topical delivery and paves way towards an efficient topical formulation for passive transungual drug delivery.     

The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14.

Human liver glycogen phosphorylase deficiency, also known as glycogen storage disease type VI (GSD VI) or Hers disease, is characterized by hepatomegaly and reduced or absent glycogenolytic response to the injection of glucagon. The recently isolated cDNA encoding the liver isozyme of glycogen phosphorylase was used to map the gene and identify restriction-fragment polymorphisms in normal Caucasians as a prerequisite for detecting linked GSD VI abnormalities. Results of restriction-enzyme analysis using a downstream fragment of the liver glycogen phosphorylase cDNA indicated the existence of a single gene copy per haploid genome. Hybridization of this downstream liver phosphorylase probe to dual laser-excited, sorted human chromosomes localized the gene to human chromosome 14. When the downstream probe was tested on genomic DNA cut with seven different restriction enzymes, a single MspI restriction-fragment-length polymorphism (RFLP) was observed in a single individual. In contrast, similar Southern blots performed with an upstream portion of the cDNA encoding liver phosphorylase revealed common RFLPs for four of eight enzymes tested, with minor polymorphic allele frequencies ranging from 33% to 44%. One of the four enzymes (TaqI) revealed two independent polymorphisms. If random distribution of these haplotypes among normal and disease loci, is assumed, approximately 92% of fetuses at risk for Hers disease will be informative when tested with the upstream liver phosphorylase probe.     

Functionality of the S-layer protein from the probiotic strain <Emphasis Type="Italic">Lactobacillus helveticus</Emphasis> M92

The objective of this study was the characterisation of the S-layer protein (SlpA) and its functional role in the probiotic activity of Lactobacillus helveticus M92. SlpA was isolated and identified by SDS-PAGE LC-MS/MS analysis. The slpA gene encoding the SlpA from L. helveticus M92 was sequenced and compared with other well characterised slpA genes. Sequence similarity searches revealed high homology with the SlpA of Lactobacillus strains. Purified SlpA showed significantly better immunomodulatory effects in orally immunised mice than L. helveticus M92 cells after SlpA removal. SlpA is involved in the autoaggregation of L. helveticus M92 cells and coaggregation of L. helveticus M92 with S. Typhimurium FP1 as these processes were negatively affected after SlpA removal from the cell surface. Therefore, the influence of oral treatment with L. helveticus M92 on an oral infection of mice by S. Typhimurium FP1 was investigated. Following the oral immunization of mice, with viable L. helveticus M92 and S. Typhimurium FP1 cells, the concentration in the luminal contents of total S-IgA and specific anti-Salmonella S-IgA antibodies, from all immunized mice was significantly higher compared to the control group or a group of mice infected only with S. Typhimurium FP1. These results demonstrate that the observed reduced infection by S. Typhimurium FP1 in mice with L. helveticus M92 is associated with competitive exclusion in the intestinal tract and enhanced immune protection conferred by the L. helveticus M92 and its SlpA.     

Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase

The intron/exon organization of the human gene for glycogen phosphorylase has been determined. The segments of the polypeptide chain that corresponds to the 19 exons of the gene are examined for relationships between the three-dimensional structure to the protein and gene structure. Only weak correlations are observed between domains of phosphorylase and exons. The nucleotide binding domains that are found in phosphorylase and other glycolytic enzymes are examined for relationships between exons of the genes and structures of the domains. When mapped to the three-dimensional structures, the intron/exon boundaries are shown to be widely distributed in this family of protein domains.     

Parasites of fishes in the recently inundated ephemeral Lake Liambezi,Namibia

Lake Liambezi forms the periodic connection between the upper Zambezi, Kwando and Okavango rivers. A full parasitological assessment was conducted on 86 fish, representing 14 species in six families sampled in August 2011. Parasite diversity was low and dominated by species with complex life cycles involving intermediate hosts. Most prevalent were larval nematodes (Contracaecum sp.) infecting 12 and Trypanasoma sp. infecting nine of the 14 host species. The intra-erythrocytic parasite Babesiosoma mariae was found in the blood of Coptodon rendalli and Oreochromis andersonii with prevalence of 50% and 60%, respectively. The host-specific monogenean Annulotrema hepseti was recorded only from H. cuvieri with a prevalence of 100%. Notable absences were the copepod and branchiuran parasites that have direct lifecycles and usually occur in high prevalence and abundance in the region. Because parasites with direct life cycles can only be transported into the lake on the host fish, their absence suggests limited immigration of infected fishes into the lake. This suggests that internal recruitment dominates over immigration in the fish population dynamics in Lake Liambezi.     

Spot-blot analysis of sorted chromosomes assigns a fructose intolerance disease locus to chromosome 9

The aldolase B gene was mapped to chromosome 9 using a rapid gene mapping system. This system uses a dual-laser sorter to identify and separate metaphase human chromosomes stained with either DIPI-chromomycin or Hoechst-chromomycin. Chromosome panels were constructed from a normal cell line by sorting 22 chromosome fractions directly onto nitrocellulose filters. Twelve labeled gene probes hybridized to the sorted chromosomal DNA fractions predicted by previous chromosome assignments. Eighteen newly cloned genes have been mapped using the same protocol.     

Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action in vivo and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.