Exercise-Induced Abdominal Wall Muscle Injury Resulting in Rhabdomyolysis and Mimicking an Acute Abdomen.

BACKGROUND: Rhabdomyolysis is characterized by muscle necrosis and release of intracellular constituents, causing muscle pain, weakness, and myoglobinuria. This can be attributed to muscle injury after strenuous exercise. If the abdominal wall is involved, clinical presentation may resemble an acute abdomen. CASE: A 27-year-old woman, gravida 4 para 2, presented with swelling and pain of the mons pubis and abdominal pain after intense powerlifting 2 days prior. A computed tomography scan was performed, revealing abdominal wall inflammation. Although myoglobinuria was absent, there was high suspicion for rhabdomyolysis, which was confirmed by an elevated creatine kinase level. The patient improved after receiving intravenous fluids and abstaining from physical activity. CONCLUSION: Abdominal wall muscle injury resulting in rhabdomyolysis can imitate an acute abdomen in a healthy woman presenting with abdominal pain and swelling.

Double Aneuploidy Detected by Cell-Free DNA Testing and Confirmed by Fetal Tissue Analysis.

BACKGROUND: Double aneuploidies account for 0.21-2.8% of spontaneous abortions resulting from chromosomal abnormalities. Rarely, cell-free DNA testing detects multiple aneuploidies; however, to discern among maternal, placental, and fetal origin, further evaluation is required. CASE: A 49-year-old woman, gravida 5 para 0, underwent cell-free DNA testing at 11 4/7 weeks of gestation, which revealed a fetus that was high risk for trisomies 18 and 21. On ultrasonography at 14 weeks of gestation, she was diagnosed with a missed abortion and underwent surgical management. Fetal and placental tissues were sent for analysis and were positive for trisomies 18 and 21, confirming the results of cell-free DNA testing. CONCLUSION: Our case highlights the ability of cell-free DNA testing to recognize a double aneuploidy confirmed by fetal tissue analysis.

Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic.

Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to inhibit the alternative pathway of complement. Here, we report the identification of the surface-associated protein SdrE as a fH-binding protein using purified fH overlay of S. aureus fractionated cell wall proteins and fH cross-linking to S. aureus followed by mass spectrometry. Studies using recombinant SdrE revealed that rSdrE bound significant fH whether from serum or as a purified form, in both a time- and dose-dependent manner. Furthermore, rSdrE-bound fH exhibited cofactor functionality for factor I (fI)-mediated cleavage of C3b to iC3b which correlated positively with increasing amounts of fH. Expression of SdrE on the surface of the surrogate bacterium Lactococcus lactis enhanced recruitment of fH which resulted in increased iC3b generation. Moreover, surface expression of SdrE led to a reduction in C3-fragment deposition, less C5a generation, and reduced killing by polymorphonuclear cells. Thus, we report the first identification of a S. aureus protein associated with the staphylococcal surface that binds factor H as an immune evasion mechanism.

Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus.

BACKGROUND: Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. METHODS: The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. RESULTS: Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. CONCLUSIONS: These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological control of S. aureus. Mass spectrometric analysis reveals that the glycation state of C3 is the same regardless of glucose concentration over a one-hour time period. However, in conditions of elevated glucose C3 appears to undergo structural changes.

Protease inhibitors decrease IgG shedding from Staphylococcus aureus, increasing complement activation and phagocytosis efficiency.

Staphylococcus aureus is a major pathogen for immunologically intact humans and its pathogenesis is a model system for evasion of host defences. Antibodies and complement are essential elements of the humoral immune system for prevention and control of S. aureus infections. The specific hypothesis for the proposed research is that S. aureus modifies humoral host defences by cleaving IgG that has bound to the bacterial surface, thereby inhibiting opsonophagocytosis. S. aureus was coated with pooled, purified human IgG and assayed for the shedding of cleaved IgG fragments using ELISA and Western blot analysis. Surface-bound IgG was shed efficiently from S. aureus in the absence of host blood proteins. Broad-spectrum protease inhibitors prevented cleavage of IgG from the S. aureus surface, suggesting that staphylococcal proteases are responsible for IgG cleavage. Serine protease inhibitors and cysteine protease inhibitors decreased the cleavage of surface-bound IgG; however, a metalloprotease inhibitor had no effect. Using protease inhibitors to prevent the cleavage of surface-bound IgG increased the binding of complement C3 fragments on the surface of S. aureus, increased the association with human neutrophils and increased phagocytosis by human neutrophils.

A comparison of antibacterial activity against Methicillin-Resistant Staphylococcus aureus and gram-negative organisms for antimicrobial compounds in a unique composite wound dressing.

OBJECTIVE: Antibiotic resistance is increasing among organisms that commonly cause wound infections. Therefore, it becomes increasingly desirable to prevent wound infections as systemic antibiotic treatment of established wound infections becomes more difficult, more expensive, and potentially more toxic. The ability to incorporate antimicrobial compounds into modern wound dressings provides an opportunity to prevent wound infections without the risk of systemic toxicity, thus diminishing morbidity, mortality, and cost to the healthcare system. DESIGN: In these studies, the authors tested 16 antimicrobial agents in a unique composite wound dressing (TheraGauze; Soluble Systems, LLC, Newport News, Virginia) against clinical methicillin-resistant Staphylococcus aureus isolates and Gram-negative organisms commonly associated with wound infections and antibiotic resistance. Disk diffusion susceptibility testing is used to quantify antimicrobial activity. RESULTS: Broad-spectrum antimicrobial activity was found for the following agents in the composite wound dressing: hydrogen peroxide, tobramycin, chlorhexidine digluconate, chlorhexidine gluconate, levofloxacin, and silver. CONCLUSION: These studies suggest that potent local antibacterial activity can be achieved with several antimicrobials in this wound dressing.

Clumping factor A interaction with complement factor I increases C3b cleavage on the bacterial surface of Staphylococcus aureus and decreases complement-mediated phagocytosis.

The human complement system is important in the immunological control of Staphylococcus aureus infection. We showed previously that S. aureus surface protein clumping factor A (ClfA), when expressed in recombinant form, bound complement control protein factor I and increased factor I cleavage of C3b to iC3b. In the present study, we show that, compared to the results for the wild type, when isogenic ClfA-deficient S. aureus mutants were incubated in serum, they bound less factor I, generated less iC3b on the bacterial surface, and bound fewer C3 fragments. It has been shown previously that two amino acids in ClfA (P(336) and Y(338)) are essential for fibrinogen binding. However, S. aureus expressing ClfA(P336A Y338S) was less virulent than ClfA-deficient strains in animal models. This suggested that ClfA contributed to S. aureus virulence by a mechanism different than fibrinogen binding. In the present study, we showed that S. aureus expressing ClfA(P336A Y338S) was more susceptible to complement-mediated phagocytosis than a ClfA-null mutant or the wild type. Unlike ClfA, ClfA(P336A Y338S) did not enhance factor I cleavage of C3b to iC3b and inhibited the cofactor function of factor H. Fibrinogen enhanced factor I binding to ClfA and the S. aureus surface. Twenty clinical S. aureus strains all expressed ClfA and bound factor I. High levels of factor I binding by clinical strains correlated with poor phagocytosis. In summary, our results suggest that the interaction of ClfA with factor I contributes to S. aureus virulence by a complement-mediated mechanism.