Transfusion-related Plasmodium ovale malaria complicated by acute respiratory distress syndrome (ARDS) in a non-endemic country

46year old female presented with a one week history of high grade fever, chills, cough, and severe nausea. The patient had been admitted a month earlier with severe lower gastrointestinal bleeding from hemorrhoids necessitating transfusion of 7 units of packed red blood cells. Initial work-up was unremarkable. Because of persistent symptoms, the patient was admitted 2 days later. Malaria smear was positive. Due to the severity of her symptoms, she was managed as falciparum malaria and was started on intravenous quinine and oral doxycycline. On the second day of treatment the patient developed respiratory failure, requiring intubation and ventilatory support with new bilateral pulmonary infiltrates. Antimalarial treatment was continued for a total of 7 days followed by primaquine for 14 days once the blood smear results revealed Plasmodium ovale infection. The patient remained intubated in the intensive care unit (ICU) for 16 days, and was later extubated successfully with a clear chest x-ray after a total of one month hospitalization. To our knowledge, this is the first case of acute respiratory distress syndrome (ARDS) secondary to blood transfusion related P. ovale malaria infection in a non-endemic country.     

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Streptococcus pneumoniae is a persistent, opportunistic commensal of the human nasopharynx and is the leading cause of community-acquired pneumonia. It expresses an anti-phagocytic capsular polysaccharide (PS). Genetic variation of the capsular PS synthesis (cps) locus is the molecular basis for structural and antigenic heterogeneity of capsule types (serotypes). Serogroup 6 has four known members (6A–6D) with distinct serologic properties, homologous cps loci, and structurally similar PSs. cps of serotypes 6A/6B have wciNα, encoding α-1,3-galactosyltransferase, whereas serotypes 6C/6D have wciNβ encoding α-1,3-glucosyltransferase. Two atypical serogroup 6 isolates (named 6X11 and 6X12) have been discovered recently in Germany. Flow cytometric studies using monoclonal antibodies show that 6X11 has serologic properties of 6B/6D, whereas 6X12 has 6A/6C. NMR studies of their capsular PSs revealed that 6X11 and 6X12 have two different repeating units with a distribution of ∼40:60 6B:6D and 75:25 6A:6C PS, respectively. Sequencing of the wciNα gene in 6X12 and 6X11 revealed single and double nucleotide substitutions, respectively, resulting in the amino acid changes A150T and D38N. Substitution of alanine with threonine at position 150 in a 6A strain was associated with hybrid serologic and chemical profiles like 6X12. The hybrid serotypes represented by 6X12 and 6X11 strains are now named serotypes 6F and 6G. Single amino acid changes in cps genes encoding glycosyltransferases can alter substrate specificities, permit biosynthesis of heterogeneous capsule repeating units, and result in new hybrid capsule types that may differ in their interaction with the immune system of the host.     

Gaining insight into the chemistry of lipoxygenases: a computational investigation into the catalytic mechanism of (8R)-lipoxygenase

Lipoxygenases (LOXs) are ubiquitous in nature and catalyze a range of life-essential reactions within organisms. In particular they are critical to the formation of eicosanoids, which are critical for normal cell function. However, a number of important questions about the reactivity and mechanism of these enzymes still remain. Specifically, although the initial step in the mechanism of LOXs has been well studied, little is known of subsequent steps. Thus, with use of a quantum mechanical/molecular mechanical approach, the complete catalytic mechanism of (8R)-LOX was investigated. The results have provided a better understanding of the general chemistry of LOXs as a whole. In particular, from comparisons with soybean LOX-1, it appears that the initial proton-coupled electron transfer may be very similar among all LOXs. Furthermore, LOXs appear to undergo multistate reactivity where potential spin inversion of an electron may occur either in the attack of O₂ or in the regeneration of the active site. Lastly, it is shown that with the explicit modeling of the environment, the regeneration of the active center likely occurs via the rotation of the intermediate followed by an outer-sphere $\rm{H^\cdot}$ transfer as opposed to the formation of a “purple intermediate” complex.     

Treatment of mercury vapor toxicity by combining deferasirox and deferiprone in rats

The hypothesis that combination of deferasirox and deferiprone chelators might be more efficient as combined therapy than single therapy in removing mercury from the body was considered. Male Wistar rats were exposed to mercury vapor for 2 weeks. After mercury administration some abnormal clinical signs such as red staining around the eyes, greenish mottling on the liver, weakness, loss of hair and weight, were observed in animals. Chelators were given orally after mercury vapor application for 2 weeks. Mercury toxicity symptoms in rats decreased after drug administration. After chelation therapy, these rats were anesthetized with ether vapor and immobilized by cervical dislocation and then their heart, liver, kidneys, intestine, spleen and testicles were sampled for determination of mercury and iron concentration. The combined chelation therapy results showed that these chelators are able to remove mercury from the body and toxicity symptoms decreased.     

Structural basis for specific inhibition of the highly sensitive ShHTL7 receptor

Striga hermonthica is a root parasitic plant that infests cereals, decimating yields, particularly in sub‐Saharan Africa. For germination, Striga seeds require host‐released strigolactones that are perceived by the family of HYPOSENSITIVE to LIGHT (ShHTL) receptors. Inhibiting seed germination would thus be a promising approach for combating Striga. However, there are currently no strigolactone antagonists that specifically block ShHTLs and do not bind to DWARF14, the homologous strigolactone receptor of the host. Here, we show that the octyl phenol ethoxylate Triton X‐100 inhibits S. hermonthica seed germination without affecting host plants. High‐resolution X‐ray structures reveal that Triton X‐100 specifically plugs the catalytic pocket of ShHTL7. ShHTL7‐specific inhibition by Triton X‐100 demonstrates the dominant role of this particular ShHTL receptor for Striga germination. Our structural analysis provides a rationale for the broad specificity and high sensitivity of ShHTL7, and reveals that strigolactones trigger structural changes in ShHTL7 that are required for downstream signaling. Our findings identify Triton and the related 2‐[4‐(2,4,4‐trimethylpentan‐2‐yl)phenoxy]acetic acid as promising lead compounds for the rational design of efficient Striga‐specific herbicides.     

Advances in Chemistry and Bioactivity of the Genus Chisocheton Blume

Chisocheton is one of the genera of the family Meliaceae and consists of ca. 53 species; the distribution of most of those are confined to the Indo‐Malay region. Species of broader geographic distribution have undergone extensive phytochemical investigations. Previous phytochemical investigations of this genus resulted in the isolation of mainly limonoids, apotirucallane, tirucallane, and dammarane triterpenes. Reported bioactivities of the isolated compounds include cytotoxic, anti‐inflammatory, antifungal, antimalarial, antimycobacterial, antifeedant, and lipid droplet inhibitory activities. Aside from chemistry and biological activities, this review also deals briefly with botany, distribution, and uses of various species of this genus.     

Polyhydroxyalkanoates: Current applications in the medical field

Polyhydroxyalkanoates (PHAs) are a class of biopolyesters that are synthesized intracellularly by microorganisms, mainly by different genera of eubacteria. These biopolymers have diverse physical and chemical properties that also classify them as biodegradable in nature and make them compatible to living systems. In the last two decades or so, PHAs have emerged as potential useful materials in the medical field for different applications owing to their unique properties. The lower acidity and bioactivity of PHAs confer them with minimal risk compared to other biopolymers such as poly-lactic acid (PLA) and poly-glycolic acid (PGA). Therefore, the versatility of PHAs in terms of their non-toxic degradation products, biocompatibility, desired surface modifications, wide range of physical and chemical properties, cellular growth support, and attachment without carcinogenic effects have enabled their use as in vivo implants such as sutures, adhesion barriers, and valves to guide tissue repair and in regeneration devices such as cardiovascular patches, articular cartilage repair scaffolds, bone graft substitutes, and nerve guides. Here, we briefly describe some of the most recent innovative research involving the use of PHAs in medical applications. Microbial production of PHAs also provides the opportunity to develop PHAs with more unique monomer compositions economically through metabolic engineering approaches. At present, it is generally established that the PHA monomer composition and surface modifications influence cell responses.PHA synthesis by bacteria does not require the use of a catalyst (used in the synthesis of other polymers), which further promotes the biocompatibility of PHA-derived polymers.