Staphylococcus aureus strains isolated from bovine mastitis: virulence,antibody production and protection from challenge in a mouse model

Septic arthritis in mice was used as a model to evaluate the virulence of Staphylococcus aureus and coagulase-negative staphylococci (CNS) isolated from cases of bovine mastitis. In addition, the model was used to evaluate the cross protection elicited by heterologous antibodies. Mice were intramuscularly inoculated with serial bacterial doses of different strains of S. aureus or CNS, for virulence determination; they were monitored for arthritis, gangrene or death up to 20 days. Antibody response, cross reactivity and resistance to challenge were tested by subcutaneous inoculation with a low dose of one of the S. aureus or CNS strains followed by challenge with two S. aureus strains. S. aureus alpha-hemolysin isolate was the most virulent, followed by alpha+beta-hemolysin and beta-hemolysin isolates. The least virulent isolates were the non-hemolytic S. aureus strains but even they were more virulent than the CNS strains tested. Antibodies against three different S. aureus antigens were detected by the ELISA in all mice that were inoculated with the S. aureus strains but not in any of those with the CNS strains. Immunoblot test against various S. aureus strains as antigens showed high cross-reactivity among the S. aureus strains but only a slight similarity, restricted to the bands above 36 kDa, with the CNS sera. Low-dose inoculation of alpha or alpha+beta strains before challenge with homologous and heterologous strains protected the mice, whereas the two beta strains provided only partial protection. The inoculations of non-hemolytic S. aureus or the CNS strains did not elicit any protection. Our findings demonstrate that pre-exposure of mice to a low dose of certain S. aureus strains could provide protection and that the antibodies produced could have an important protective role.     

The screens culture: impact on ADHD

Children's use of electronic media, including Internet and video gaming, has increased dramatically to an average in the general population of roughly 3?h per day. Some children cannot control their Internet use leading to increasing research on "internet addiction." The objective of this article is to review the research on ADHD as a risk factor for Internet addiction and gaming, its complications, and what research and methodological questions remain to be addressed. The literature search was done in PubMed and Psychinfo, as well as by hand. Previous research has demonstrated rates of Internet addiction as high as 25% in the population and that it is addiction more than time of use that is best correlated with psychopathology. Various studies confirm that psychiatric disorders, and ADHD in particular, are associated with overuse, with severity of ADHD specifically correlated with the amount of use. ADHD children may be vulnerable since these games operate in brief segments that are not attention demanding. In addition, they offer immediate rewards with a strong incentive to increase the reward by trying the next level. The time spent on these games may also exacerbate ADHD symptoms, if not directly then through the loss of time spent on more developmentally challenging tasks. While this is a major issue for many parents, there is no empirical research on effective treatment. Internet and off-line gaming overuse and addiction are serious concerns for ADHD youth. Research is limited by the lack of measures for youth or parents, studies of children at risk, and studies of impact and treatment.     

Camels' milk: for drinking only?

Camels' milk, women's milk and cows' milk were kept at 30 degrees C and refrigerated at 4 degrees C. This explains the necessity to immediately freeze milk if it needs to be kept even for a few days. Cows' milk remained good for days if stirred and then turned sour, enabling the making of cheeses and butter. Camels' milk did not sour at 4 degrees C for up to 3 months. This means that camels' milk is mainly good only for drinking, as was promised to this animal by the Prophet.     

Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci

Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and susceptibility to skin carcinogenesis respectively, show significant linkage disequilibrium (LD) at genetic markers mapping on chromosomal regions where skin cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively) have been mapped in standard crosses. Analysis of these regions for genetic linkage with skin cancer phenotypes in 245 (Car-R × Car-S)F₂ intercross mice, by using single nucleotide polymorphisms (SNPs), revealed significant linkage at a possible allelic form of the Skts1 locus, whose mapping region was shortened to a <5.5-cM interval near the Tyr locus. The Car-derived Skts1 locus was linked with papilloma multiplicity and latency by a recessive inheritance of the susceptibility allele. Putative loci on Chr 5 (Skts3) and 9 (Psl1) showed no significant linkage. These results point to the important role of the Stks1 locus in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes. Received: 23 June 2000 / Accepted: 22 November 2000     

To what end does nature produce superoxide? NADPH oxidase as an autocrine modifier of membrane phospholipids generating paracrine lipid messengers

Production of superoxide anion O2<sup>••- by the membrane-bound enzyme NADPH oxidase of phagocytes is a long-known phenomenon; it is generally assumed that O2• kill bacterial intruders. The details and the chemistry of the killing process have, however, remained a mystery. Isoforms of NADPH oxidase exist in membranes of nearly every cell, suggesting that reactive oxygen species (ROS) participate in intra- and intercellular signaling processes. What the nature of the signal is exactly, how it is transmitted, and what structural characteristics a receptor of a "radical message" must have, have not been addressed convincingly. This review discusses how the action of messengers is in agreement with radical-specific behavior.

In search for the smallest common denominator of cellular free radical activity we hypothesize that O2•e acid, HO2&bull under primordial conditions as regulators of membrane mechanics and that isoprostanes, widely used markers of "oxidative stress", may be an adventitious correlate of this biologic activity of O2•location="post" arrange="compact">2&bullre is presented that suggests that O2•location="post" arrange="compact">2&bullfying cell membranes, help other agents gain access to the hydrophobic region of phospholipid bilayers and hence contribute to lipid-dependent signaling cascades. With this, O2•location="post" arrange="compact">2&bullndispensable adjuvants for the generation of cellular signals, for membrane transport, channel gating and hence, in a global sense, for cell viability and growth. We also suggest that many of the allegedly O2•ial pathologies and carcinogenic derailments are due to membrane-modifying activity rather than other chemical reactions of O2•location="post" arrange="compact">2&bull this picture is the potential evolution of the "radical theory of ageing" to a "lipid theory of aging".</sup>     

Activity and conformation of a cyclic heptapeptide possessing the message sequence His-Phe-Arg-Trp of alpha-melanotropin

Alpha-melanotropin (alpha-MSH, i.e. alpha-melanocyte stimulating hormone), tridecapeptide (Ac-Ser(1)-Tyr-Ser-Met-G1u(5)-His-Phe-Arg-Trp-Gly(10)-Lys-Pro-Val(13)-NH(2)), has been extensively studied to understand structure-activity relationships. The core sequence (His-Phe-Arg-Trp) is conserved in several species and is considered as the primary active site or "message sequence". Attempts have been made to design conformationally constrained cyclic analogs containing the message sequence to improve the activity. We had earlier reported that the cyclic analog--cyclo[Gly-His-D-Phe-Arg-Trp-Gly], a 18 membered ring system with two fused beta-turn structure, was less active than the corresponding linear peptide. It was suggested that ring size could be an important parameter in the activity of cyclic melanotropic analogs. To investigate the effect of ring size on biological activity, a cyclic heptapeptide, cyclo[Nle(1)-Gly-His-D-Phe-Arg(5)-Trp-Gly(7)], with 21 member ring system was synthesized. This peptide has three orders of magnitude higher biological activity than the cyclic hexapeptide. The conformational study of this cyclic heptapeptide in DMSO-d(6) by NMR and molecular dynamics simulations reveals a structure with two fused beta-turns running across the residues D-Phe(4)-Gly(7) (Type I) and Gly(7)-His(3) (Type II). These findings confirm that stabilization of beta-turns and a relatively larger ring size are essential determinants of activity for cyclic alpha-MSH analogs.