Novel combined pharmacological strategy to alleviate acute phase response following zoledronic acid treatment.

Brief rationale: Zoledronic acid treatment against osteoporosis is limited by APR. Main result: Combination therapy (hydrocortisone plus non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone) reduced intolerable APR levels and provided complete symptom relief in most patients. Significance of the paper: Combination therapy can enhance patient outcomes in osteoporosis management. PURPOSE: Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms. METHODS: A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test. RESULTS: There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases. CONCLUSION: The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management.

The effect of methionine supplementation on receiving beef steers following a lipopolysaccharide challenge.

The objective of this study was to evaluate the effects of methionine supplementation prior to and during a lipopolysaccharide (LPS) challenge on the performance and inflammatory biomarkers of receiving beef steers. Steers (n = 65; 295.8 ±â€…46.5 kg) were randomly assigned to 3 treatment groups: L0 = Control, receiving no supplement; L1 = 10 g/hd/d rumen-protected methionine (MetaSmart, Adisseo USA Inc., Alpharetta, GA); and L2 = 20 g/hd/d rumen-protected methionine and fed for 40 d at the West Texas A&M University Research Feedlot. On day 40, a subset of steers (n = 32; L0 = 10; L1 = 11; L2 = 11) were transported to the USDA Livestock Issues Research Unit, and on day 41 steers were weighed and fitted with indwelling rectal thermometers and jugular catheters. On day 42, steers were challenged i.v. with LPS (0.25 µg/kg BW). Blood samples were collected at -2, 0, 2, 4, 6, 8, 10, 12, 18, 24, 36, and 48 h relative to the LPS administration at 0 h. Serum was isolated to determine serum chemistry and inflammatory marker concentrations. Whole blood was used for hematology analysis. There were no differences in DMI or ADG (P ≥ 0.75) during 35 d of supplementation. A treatment × time interaction (P = 0.01) occurred for rectal temperature, where L2 steers had the greatest temperature following the challenge (P ≤ 0.05) compared to L1 and L0 steers. There was a treatment × time interaction (P = 0.03) for the change in white blood cells where L0 steers had the greatest change compared to L1 and L2 steers at various timepoints. There was a treatment × time interaction (P = 0.02) for the change in tumor necrosis factor-α concentration, where there was a greater increase in concentration in L0 compared to L1 and L2 steers. Additionally, there was a treatment × time interaction (P < 0.01) for Macrophage Inflammatory Protein-1ß (MIP-1ß) concentrations, where concentrations were greater in L0 compared with L1 and L2 steers from 2 to 4 h post-challenge. There was a treatment × time interaction for plasma total protein concentration (P < 0.01) where L0 steers had less plasma total protein compared with L1 and L2 steers, while L1 steers had less plasma total protein than L2 steers at -2 h prior to LPS challenge. These data suggest that methionine supplementation may have an immunomodulatory effect in beef steers that may improve response to pathogens.

Acute exercise-induced inflammatory and thrombotic response in hypertensive patients.

PURPOSE: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. METHODS: After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured. RESULTS: All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%). CONCLUSION: In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.

A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis.

Regulation of fibrinogen synthesis.

The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bß, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric "dimer of trimers" (AαBßγ)2. Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein. Fibrinogen is one of the most prevalent coagulation proteins in blood, and its expression is induced by inflammatory cytokines, wherein circulating fibrinogen levels may increase up to 3-fold during acute inflammatory events. Abnormal levels of circulating fibrinogen are associated with bleeding and thrombotic disorders, as well as several inflammatory diseases. Notably, therapeutic strategies to modulate fibrinogen levels have shown promise in experimental models of disease. Herein, we review pathways mediating fibrinogen synthesis, from gene expression to secretion. Knowledge of these mechanisms may lead to the identification of biomarkers and new therapeutic targets to modulate fibrinogen in health and disease.

Acute phase response and oxidative stress in coccidiosis: A review in domestic animals.

Coccidiosis is a highly significant disease in domestic animals due to its global distribution and economic impact. The occurrence of oxidative stress (OS) and the acute phase response (APR) play crucial roles in the development of coccidiosis, thereby contributing to the pathogenicity of coccidia. A range of triggers including parasitic infection, can induce the APR. This response encompasses a set of hormonal and metabolic changes to restore body stability and improve the body's healing capabilities. Ovine coccidiosis has the potential to cause OS, which can be prevented and treated through the use of dietary additives. By including Curcuma longa in the diets of infected sheep, it is possible to reduce lipid peroxidation (LPO) and nitric oxide (NO) production, while simultaneously improving serum antioxidant capacity and interleukin-10 (IL-10) levels. Caprine coccidiosis can activate the APR. Research indicated that goats suffering from coccidiosis exhibited elevated concentrations of malondialdehyde (MDA) and total homocysteine, along with reduced levels of some enzymes such as superoxide dismutase (SOD) and glutathione reductase (GR), as well as decreased levels of zinc (Zn), manganese (Mn), selenium (Se), vitamin C, and total antioxidant capacity (TAC). Bovine coccidiosis is linked to elevated MDA concentrations and reduced serum glutathione (GSH) and TAC levels. Eimeria can induce OS and inflammatory damage in infected birds by releasing pro-inflammatory mediators from cells, resulting in a significant increase in CAT and SOD activity, lipid peroxidation and damage to the intestinal epithelium. To promote the antioxidant system of infected birds, some herbal food additives such as grape seed proanthocyanidine extract, Curcuma longa and Rumex nervosus leaf extract, can be used. Research on the APR in birds is not as extensive as in ruminants. Currently, there is a lack of studies on the occurrence of OS and APR in camels, horses, dogs, and cats with coccidiosis.

Zinc Deficiency in Critically Ill Patients: Impact on Clinical Outcome.

Background Zinc is a trace element essential for the normal functioning of many vital enzymes and organ systems. Studies examining the rates and degrees of zinc deficiency and its consequences in patients with critical illnesses remain scarce. Materials and methods This is a prospective observational study assessing zinc deficiency in critically ill adult patients admitted to a tertiary care intensive care unit (ICU) and its impact on clinical outcomes. Patients were divided into those with normal (≥ 71 µg/dl) and low (≤ 70 µg/dl) zinc levels. Zinc-deficient patients were further divided into mild, moderate, and severe zinc deficiency groups based on zinc levels of 61-70 µg/dl, 51-60 µg/dl, and below 51 µg/dl, respectively. The primary outcome assessed was ICU mortality, and the secondary outcomes were ICU length of stay (LOS), duration of invasive mechanical ventilation (IMV), acute kidney injury (AKI) at admission, need for non-invasive ventilation (NIV), renal replacement therapy (RRT), or vasopressors during the course of the ICU. Other parameters compared included APACHE (Acute Physiology and Chronic Health Evaluation) II, SOFA (Sequential Organ Failure Assessment) score on day 1, and levels of lactate, procalcitonin, calcium, magnesium, phosphate, and serum albumin. The study also compared the mean zinc levels in patients with low and high SOFA scores (scores up to 7 vs. 8 and above) and low and high APACHE II values (scores up to 15 vs. 16 and above). Results A total of 50 patients were included, of whom 43 (86%) were zinc deficient. Mortality in zinc-deficient and normal zinc-level patients was 33% and 43%, respectively (p = 0.602). Patients with zinc deficiency were also older (mean age 69 vs. 49 years, p = 0.02). There was no difference in secondary outcome parameters, except for more zinc-deficient patients needing RRT. Twenty-six of the zinc-deficient patients had severe zinc deficiency, ten moderate, and seven mild (p = 0.663). ICU mortality was approximately 42%, 10%, and 29% in the severe, moderate, and mild deficiency groups, respectively (p = 0.092). Zinc levels were similar between those with low and high APACHE II scores (mean 47.9 vs. 45.5 µg/dl, p = 0.606) as well as between low and high SOFA scores (mean 47.8 vs. 45.7 µg/dl, p = 0.054). Conclusion The present study suggests that zinc deficiency is very common in critically ill patients but does not correlate with their severity of illness, nor does it lead to a poorer outcome in these patients. However, further studies with a larger cohort of patients would be required to make definitive conclusions.

Effects of multi-walled carbon nanotubes on gene and microRNA expression in human hepatocarcinoma HepG2 cells.

The usage of multi-walled carbon nanotubes (MWCNT) has increased exponentially in the past years, but, potential toxicity mechanisms are not clear. We studied the transcriptomic alterations induced by one multi-walled carbon nanotube (MWCNT) and its -OH and -COOH functionalized derivatives in human HepG2 cells. We showed that all three MWCNT treatments induced alterations in stress-related signaling pathways, inflammation-related signaling pathways, cholesterol synthesis pathways, proliferation-related pathways, senescence-related pathways and cancer-related pathways. In stress-related pathways, the acute phase response was induced in all three MWCNTs and all doses treated and ranked high. Other stress-related pathways were also related to the oxidative-induced signaling pathways, such as NRF-2 mediated oxidative stress response, hepatic fibrosis/Stella cell activation, iNOS signaling, and Hif1α signaling. Many inflammation-related pathways were altered, such as IL-8, IL-6, TNFR1, TNFR2, and NF-κB signaling pathways. These results were consistent with our previous results with exposures to the same three multi-walled carbon nanotubes in human lung BEAS-2B and also with results in mice and rats. From the microRNA target filter analysis, TXNIP & miR-128-3p interaction was present in all three MWCNT treatments, and maybe important for the induction of oxidative stress. CXCL-8 & miR-146-5p and Wee1 & miR-128-3p were only present in the cells treated with the parent and the OH-functionalized MWCNTs. These mRNA-miRNA interactions were involved in oxidative stress, inflammation, cell cycle, cholesterol biosynthesis and cancer related pathways. Target filter analysis also showed altered liver hyperplasia/hyperproliferation and hepatic cancer pathways. In short, target filter analysis complemented the transcriptomic analysis and pointed to specific gene/microRNA interactions that can help inform mechanism of action. Moreover, our study showed that the signaling pathways altered in HepG2 cells correlated well with the toxicity and carcinogenicity observed in vivo, indicating that HepG2 may be a good in vitro predictive model for MWCNT toxicity studies.

New Regulatory roles for Human Serum Amyloid A.

The current study illuminates the multifaceted role of Serum Amyloid A (SAA), an essential acute-phase protein implicated in diverse biological realms, encompassing inflammation, oncogenesis, and stress modulation. With a focus on delineating the intricate protein-protein interactions orchestrated by SAA, this investigation unravels its diverse functions within the human physiological landscape. Utilizing the HepG2 cell line, renowned for its proficiency in facilitating SAA overexpression, we meticulously generated protein extracts after inducing SAA hyperexpression. Integrating Co-Immunoprecipitation techniques with Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS) enabled discernment and characterization of the protein complexes intricately associated with SAA. Our data elucidates a pronounced upregulation in SAA expression levels within induced samples compared to controls, substantiating its pivotal role among inflammatory cascades. Specifically, LC/MS/MS profiling delineated interactions with nine distinct proteins, encompassing pivotal players in actin dynamics, neuronal morphogenesis, lipid homeostasis, and immunomodulation. Furthermore, this investigation underscores the plausible ramifications of these molecular interactions in pathologies, including Alzheimer's disease, oncological manifestations, and rheumatoid arthritis. Through comprehensive analyses, this investigation sheds light on the intricate roles of SAA and provides a foundation for future therapeutic modalities targeting SAA pathologies.

Postoperative monitoring of ovariohysterectomy carried out with two types of surgical sutures in shelter cats and differences in selected blood parameters between shelter and pet cats.

BACKGROUND: Reduction of inflammation and early detection of complications after surgical procedures are important objectives for proper veterinary practice. This study aimed to evaluate the differences between shelter and pet female cats in selected acute-phase parameters scheduled to ovariohysterectomy. Postoperative monitoring after ovariohysterectomy with the same laboratory parameters was performed in shelter cats, in which two different types of surgical sutures were used for the entire procedure. The experimental group comprised 40 female cats from animal shelters ('shelter cats,' n = 40). These cats were divided into two subgroups: group A (n = 20) operated on with absorbable sutures and group NA (n = 20) operated on with non-absorbable sutures. In addition, the same parameters were evaluated in pet female cats (n = 19). Blood was collected from shelter cats immediately before surgery (term 0), at 24 and 72 h (terms 1 and 3, respectively), and at 7 and 14 days (terms 7 and 14, respectively) after ovariohysterectomy. Blood samples from the pet cat group were collected only once. RESULT: The mean haptoglobin concentration before ovariohysterectomy in pet cats was significantly lower than that in shelter cats. Fibrinogen concentration was significantly lower in pet cats than in cats from group A. Serum albumin, beta-1, beta-2, and gamma-globulin concentrations were significantly higher in the shelter cats than in the pet cats. Subcutaneous tissue thickening at the site of the postoperative wound was observed in five patients cats (25%) in group A, and two (10%) cats in the NA group. CONCLUSION: These results indicate that ovariohysterectomy leads to local and general inflammatory responses. The majority of cats from animal shelters suffered from subclinical inflammation.

Non-specific markers of inflammation in bare-nosed wombats (Vombatus ursinus) with sarcoptic mange.

Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei, negatively impacts the health, welfare, and local abundance of bare-nosed wombats (Vombatus ursinus) in Australia. Improved understanding of the host immune response to disease and its contribution to pathophysiology could be used to inform management actions for this species in and ex situ. To evaluate the immune response of bare-nosed wombats to sarcoptic mange, we validated three assays (haptoglobin, agarose gel electrophoresis, and micro-erythrocyte sedimentation rate) measuring non-specific markers of inflammation using serum samples from free-living wombats from Tasmania (n = 33). We then analysed correlations between the assay results for each non-specific marker of inflammation and wombat's sarcoptic mange scores, and performed histopathological examinations to investigate association of the acute phase response with systemic amyloidosis. We present evidence that haptoglobin and erythrocyte sedimentation rate increased, and albumin decreased, in association with sarcoptic mange scores. This research demonstrates links between the acute phase response and sarcoptic mange severity in bare-nosed wombats, highlighting the utility of non-specific markers of inflammation for aiding assessment of the systemic effects of mange. Showing the value of agarose gel electrophoresis, we also identified specific acute phase proteins warranting future evaluation and found evidence of an immunoglobulin response in mange-affected wombats, revealed by increasing γ-globulins in association with apparent disease severity. Meanwhile, owing to its relatively low resource requirements and rapidity, the erythrocyte sedimentation rate assay may be useful as a point-of-care test to support therapeutic decisions in the field. Our methods and findings are likely to be applicable to a range of other clinical and population health scenarios in captive and free-living wombats, and species impacted by sarcoptic mange globally.

Performance of an automated immunoturbidimetric assay for bovine serum amyloid A.

BACKGROUND: Acute phase proteins are a group of vital constituents of the innate immune system, which may also serve as circulatory biomarkers of inflammation. The major acute phase protein serum amyloid A (SAA) is a reliable and sensitive biomarker in cows, allowing for rapid detection of inflammatory disease. A multispecies automated immunoturbidimetric assay (VET-SAA, Eiken) has been validated for horses, dogs, and cats, and it has been used to measure SAA concentrations in bovine samples. OBJECTIVES: The aim of the present study was to perform an analytical validation of the VET-SAA immunoturbidometric assay based on monoclonal antihuman SAA antibodies for the measurement of SAA in clinical samples from cows. METHODS AND RESULTS: The validation included an assessment of imprecision, inaccuracy, and detection limit, as well as an evaluation of the overlap performance, using banked serum from healthy and sick cows with or without inflammatory disease. Intra- and interassay variation ranged from 0.91% to 2.9% and 2.5% to 5.8%, respectively. The assay was performed with acceptable accuracy within a clinically relevant range of SAA, although minor signs of inaccuracy were detected. Overlap performance was acceptable, with the VET-SAA assay able to differentiate between healthy cows and cows with inflammatory and noninflammatory conditions. The automated VET-SAA assay is considered acceptable for the measurement of SAA in cows.

Increased Erythrocyte Sedimentation Rate in Dogs: Frequency in Routine Clinical Practice and Association with Hematological Changes.

(1) Background: the erythrocyte sedimentation rate (ESR) has been reported to increase in some infectious or inflammatory diseases in dogs, but no information on the frequency of increases in a routine clinical setting exists. The aim of this study was to assess the frequency of an increased ESR in dogs and to investigate its possible association with hematologic changes; (2) Methods: A total of 295 EDTA blood samples were randomly selected from the routine caseload of the Veterinary Teaching Hospital. Samples were grouped in controls and in pathologic groups based on the clinical presentation. A routine hemogram was performed, then the ESR was measured using the instrument MINI-PET; (3) Results: compared with controls, the ESR was significantly higher in all the pathologic groups, except for the hematological disorders group. The highest ESR was found in samples from dogs with chronic kidney disease or inflammation, followed by those from dogs with mild chronic disorders, severe/acute diseases, tumors and urinary disorders. The ESR negatively correlated with hematocrit and positively with neutrophil counts. (4) Conclusions: The ESR increases more frequently in dogs with clinically evident inflammation or CKD, but also in several other conditions, likely as a consequence of anemia and acute phase response.

Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant.

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen.

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.

Physicochemical properties of 26 carbon nanotubes as predictors for pulmonary inflammation and acute phase response in mice following intratracheal lung exposure.

Carbon nanotubes (CNTs) vary in physicochemical properties which makes risk assessment challenging. Mice were pulmonary exposed to 26 well-characterized CNTs using the same experimental design and followed for one day, 28 days or 3 months. This resulted in a unique dataset, which was used to identify physicochemical predictors of pulmonary inflammation and systemic acute phase response. MWCNT diameter and SWCNT specific surface area were predictive of lower and higher neutrophil influx, respectively. Manganese and iron were shown to be predictive of higher neutrophil influx at day 1 post-exposure, whereas nickel content interestingly was predictive of lower neutrophil influx at all three time points and of lowered acute phase response at day 1 and 3 months post-exposure. It was not possible to separate effects of properties such as specific surface area and length in the multiple regression analyses due to co-variation.

Navigating the Enigma of Pediatric Musculoskeletal Infections: A Race Against Time.

Musculoskeletal infection (MSKI) in children is a critical condition in pediatric orthopedics due to the potential for serious adverse outcomes, including multiorgan dysfunction syndrome, which can lead to death. The diagnosis and treatment of MSKI continue to evolve with advancements in infectious organisms, diagnostic technologies, and pharmacologic treatments. It is imperative for pediatric orthopedic surgeons and medical teams to remain up to date with the latest MSKI practices.

Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice.

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.

The impact of inflammation and acute phase activation in cancer cachexia.

The development of cachexia in the setting of cancer or other chronic diseases is a significant detriment for patients. Cachexia is associated with a decreased ability to tolerate therapies, reduction in ambulation, reduced quality of life, and increased mortality. Cachexia appears intricately linked to the activation of the acute phase response and is a drain on metabolic resources. Work has begun to focus on the important inflammatory factors associated with the acute phase response and their role in the immune activation of cachexia. Furthermore, data supporting the liver, lung, skeletal muscle, and tumor as all playing a role in activation of the acute phase are emerging. Although the acute phase is increasingly being recognized as being involved in cachexia, work in understanding underlying mechanisms of cachexia associated with the acute phase response remains an active area of investigation and still lack a holistic understanding and a clear causal link. Studies to date are largely correlative in nature, nonetheless suggesting the possibility for a role for various acute phase reactants. Herein, we examine the current literature regarding the acute phase response proteins, the evidence these proteins play in the promotion and exacerbation of cachexia, and current evidence of a therapeutic potential for patients.

Effect of photoperiod on serum biochemistry, electrolytic balance, acute phase response and histopathology of butter catfish, Ompok bimaculatus (Bloch, 1794).

The present study was executed to evaluate the effect of photoperiod on serum biochemical parameters (glucose, cortisol, ALT, AST and LDH), electrolytic balance (Sodium and potassium), acute phase response (CRP) and histopathology (liver, kidney and skin) of an endangered high valued catfish, Ompok bimaculatus. Catfish (21.00 ± 1.53 cm and 30.00 ± 2.31 g) from the acclimatized stock were randomly distributed to six 120 × 45 × 60 cm3 FRP tanks (n = 20 fish per tank) and exposed to 1500 lx light intensity under different photoperiods [24:0 light: dark (L: D), 15L: 9D, 12L: 12D, 9L: 15D, 0L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of bodyweight, twice a day for 60 days. Serum glucose, cortisol and enzymes including aspartate transaminase (AST), lactate dehydrogenase (LDH), alanine transaminase (ALT), and acute phase reactant, such as C-reactive protein (CRP) increased significantly (P < 0.05) in continuous light (24L: 0D), continuous dark (0L: 24D) and short day (9L: 15D) photoperiods, whereas in 15L: 9D and 12L:12D photoperiods, those were in decreasing trend. Serum electrolytes, i.e. potassium level was elevated and sodium level was declined in 24L: 0D, 0L: 24D and 9L: 15D photoperiod groups. Moreover, significant histological alterations in the liver, kidney and skin tissue were also evidenced in the experimented catfish. Typical polygonal hepatocytes with normal blood vessels in liver and normal organization of kidney were seen in catfish of 15L: 9D group. Histological analysis of other groups displayed nuclear degeneration, karyorrhexis, karyolysis, melanomacrophages, nuclear hypertrophy, sinusoid dilation and vacuolar degeneration in liver and hyaline droplets accumulation, granular degeneration, fragmentation of glomerulus and focal necrosis of epithelial cells in kidney. Additionally, general structure of the skin was observed in control group as well as in 15L: 9D group. Contrarily, in 24L: 0D group increased number of mucous cells and vacuoles was observed in the skin of butter catfish. In 9L: 15D and 0L: 24D photoperiods, O. bimaculatus exhibited ruptured epithelial cells, enlarged alarm cells, fat cells, necrotic cells and vacuoles in the skin tissue. The present study depicted that 15L: 9D photoperiod can induce better health of catfish, O. bimaculatus, which, in turn, can help farmers to increase the production of this high valued catfish in future.