Equal Maintenance of Anti-SARS-CoV-2 Antibody Levels Induced by Heterologous and Homologous Regimens of the BNT162b2, ChAdOx1, CoronaVac and Ad26.COV2.S Vaccines: A Longitudinal Study Up to the 4th Dose of Booster.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

Serological and Molecular Evidence of the Circulation of the Venezuelan Equine Encephalitis Virus Subtype IIIA in Humans, Wild Vertebrates and Mosquitos in the Brazilian Amazon.

Understanding the interaction between viruses and ecosystems in areas with or without anthropic interference can contribute to the organization of public health services, as well as prevention and disease control. An arbovirus survey was conducted at Caxiuanã National Forest, Pará, Brazil, where 632 local residents, 338 vertebrates and 15,774 pools of hematophagous arthropods were investigated. Neutralization antibodies of the Venezuelan Equine Encephalitis virus, subtype IIIA, Mucambo virus (MUCV) were detected in 57.3% and 61.5% of humans and wild vertebrates, respectively; in addition, genomic fragments of MUCV were detected in pool of Uranotaenia (Ura.) geometrica. The obtained data suggest an enzootic circulation of MUCV in the area. Understanding the circulation of endemic and neglected arboviruses, such as MUCV, represents an important health problem for the local residents and for the people living in the nearby urban centers.

Absence of Anti-RBD Antibodies in SARS-CoV-2 Infected or Naive Individuals Prior to Vaccination with CoronaVac Leads to Short Protection of Only Four Months Duration.

The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45-90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

[The in vitro examination of the effectiveness of antiseptic substances for a surface disinfection of teeth inoculated with Escherichia coli]. / Issledovanie in vitro éffektivnosti antisepticheskikh veshchestv dlia poverkhnostnoi dezinfektsii zubov, inokulirovannykh Escherichia coli.

The aim of the study was to assess the possibility of penetration of Escherichia coli bacteria into the dentinal tubules of the samples and determine the antimicrobial efficacy after 5 and 20 min exposition of 3% H2O2 (groups I and II) and 1 and 5 min exposition of 3% NaOCl (groups III and IV) for surface disinfection of bovine teeth. The samples were subjected to inoculation with E. coli suspension. The quality of disinfection was assessed with the three methods. The surface disinfection of samples proved to be effective only in groups II and IV. In the cultures of all dissolutions of dentinal chips suspensions in groups I, III and V there was a growth of E. coli in the form of a continuous pitch. In the group II a growth of Escherichia coli was revealed only in the initial dissolution in the quantity 1,8x101 CFU/ml, whereas in the group IV the growth was nil. Quantitative estimation of bacterial penetration using the method of maximum dissolutions revealed similar quantity of bacteria as in the group II as well as in the calculation of CFU. The application of 3% solution of H2O2 with the exposition of 20 minutes secures the qualitative surface disinfection of teeth without destruction of bacteria inside dental tubules and that allows to discover viable bacteria inside dentinal tubules.

The influence of gene-gene and gene-environment interactions on the risk of asbestosis.

This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, and iNOS polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between MnSOD Ala -9Val polymorphism and the risk of asbestosis and between iNOS genotypes and asbestosis were modified by CAT -262 C > T polymorphism (P = 0.038; P = 0.031). A strong interaction was found between GSTM1-null polymorphism and smoking (P = 0.007), iNOS (CCTTT) n polymorphism and smoking (P = 0.054), and between iNOS (CCTTT) n polymorphism and cumulative asbestos exposure (P = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases.

Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle.

The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1α expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors.

Central FoxO3a and FoxO6 expression is down-regulated in obesity induced diabetes but not in aging.

BACKGROUND: Recent data suggest that insulin-like growth factor (IGF)-1 resistance in neurons prolongs longevity. In C. elegans this effect is mediated via DAF-16 the ortholog of the mammalian FoxO transcription factors. 3 different FoxO transcription factors (FoxOs) are expressed in rodent CNS: FoxO1, FoxO3a and FoxO6. METHODS: To define whether the different FoxOs are region-, sex- and age-specifically expressed, we analyzed FoxO mRNA levels in different brain regions from 6, 16, 60 and 100 weeks old mice using realtime-PCR. In addition, we fed mice a high fat diet (HFD) to experimentally induce obesity and diabetes and analyzed FoxO mRNA in the different brain regions. RESULTS: Interestingly, FoxO1 was predominantly expressed in the hippocampus whereas FoxO3a was quantitatively the most abundant FoxO in the neocortex. During aging, FoxO1 expression peaked in all brain regions at 16 weeks and FoxO6 showed its highest expression at 60 weeks in the parietal and occipital cortex. In 6 weeks old mice FoxO6 expression was higher in male compared to female mice in the hippocampus and all cortical regions. Surprisingly, in HFD animals FoxO3a was significantly less expressed in the cerebellum and all cortical regions compared to control animals. Even more dramatic, FoxO6 expression dropped about 80% in all brain regions in response to HFD. CONCLUSION: Thus, FoxOs in the CNS showed a highly distinct expression, which in addition was age- and sex-dependent. In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.

Critical volume model analysis of lung complication data from different strains of mice.

The critical volume (CV) normal tissue complication probability (NTCP) model was used to fit experimental data on radiation pneumonitis in mice to test the model and determine the values of the model parameters characterizing the lung structure: relative critical volume and cell radiosensitivity. The entire lungs of mice from ten different strains were irradiated acutely and homogeneously to different doses. The experimental animals from the different strains expressed different radiation sensitivities, forming ten well-defined dose-response curves. The most widely accepted biological NTCP model (the individual CV NTCP) readily applicable to cases of acute uniform irradiation was used to fit all the individual dose-response curves simultaneously. To account for the apparent difference in the response of the different strains, it was assumed that the strains differed in their (cell) radiosensitivity. The maximum likelihood method of fitting was used. The obtained fit was statistically highly acceptable. The best-fit value of the relative critical volume, mu, was 78%, which is extremely close to the histologically observed value of around 72%. The values of radiosensitivity, alpha, ranged between 0.26 and 0.37 Gy(-1) for the different strains. The best-fit numbers of functional subunits (FSU) constituting the lung, N, and the number of cells in an FSU, N(o), were implausibly low: N = 9 and N(o) = 23, respectively. The best-fit value of N(o)N was a very small number that was unlikely to correspond to the total number of cells comprising the lung, suggesting that a different interpretation of N and N(o) was required. The individual CV model provided a simultaneous description of the individual responses of different mouse strains through assumed interindividual variability in alpha only. A new interpretation is given to the entities corresponding to N(o) and N. N(o)N is interpreted as the number of certain elementary structures. These structures are considered to be equivalent to the classical functional subunit, which is much larger than a cell and plays a fundamental role in determining the radiation response of the organ. N is identified as the number of the few large subdivisions of the lungs, M = microN is the number that have to be damaged for the lung to fail. N(o) is interpreted as the mean number of elementary structures (FSU) per large subdivision. This imposes a picture of damage to large, contiguous subdivisions containing many FSU, which is consistent with the histological appearance of the lungs of mice in respiratory distress. This picture is in marked contrast to the random distribution of small areas of damage expected for the small size of an FSU. This random distribution is characteristic of earlier stages of the development of radiation pneumonitis, suggesting that some additional process spreads injury from damaged FSU to adjacent, undamaged FSU during the terminal phase.

Variation in mitochondrial function in hypoxia-sensitive and hypoxia-tolerant human glioma cells.

We have shown previously that human glioblastoma multiforme cells vary in their ability to survive under hypoxic conditions. Under oxygen limiting conditions, hypoxia-tolerant cells decrease their oxygen consumption rate whereas hypoxia-sensitive cells continue to consume oxygen at a relatively steady rate until the oxygen supply becomes exhausted. We now show that hypoxia-tolerant and hypoxia-sensitive cells exhibit distinct patterns of mitochondrial function in response to hypoxic challenge. Hypoxia-tolerant cell lines retain stable mitochondrial membrane potential and ATP concentration when incubated under oxygen limiting conditions. In addition, hypoxia-tolerant cell lines are consistently more sensitive to a wide spectrum of inhibitors of mitochondrial function than are hypoxia-sensitive cells. In contrast, the hypoxia-sensitive cells are unable to maintain stable mitochondrial membrane potential and ATP levels when incubated at reduced oxygen tension. These results demonstrate significant differences in the mitochondrial function between these two phenotypes and reinforce previous data that suggest a regulatory role for mitochondria in the development of hypoxia tolerance.

In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects.

Biolistic transmission of mRNA provides transient gene therapy to in vivo organs. This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration, cellular injury, and Green Fluorescent Protein synthesis were quantified. Chimeric human epidermal growth factor-FLAG epitope cDNA or mRNA was transmitted to wounds in normal or steroid treated animals. Wound bursting strength, human epidermal growth factor-FLAG, and collagen synthesis were determined. Injury and bullet penetration correlated with the delivery velocity and bullet size. Optimal delivery parameters were established which provided widespread Green Fluorescent Protein synthesis. Human epidermal growth factor-FLAG treatment significantly increased collagen content and wound breaking strength in normal and steroid treated animals. FLAG protein synthesis was evident in mRNA treated fascia following treatment. We found the gene gun provides a novel method for efficient, in vivo delivery of mRNA-based therapeutic strategies to mammalian organs with minimal histologic damage allowing transient expression of protein in in vivo target tissues. Co-delivery of Green Fluorescent Protein mRNA may provide a useful positive control to determine effective transmission. Biolistic transmission of human epidermal growth factor-FLAG mRNA provides increased tissue epidermal growth factor levels and accelerates wound healing in normal and steroid exposed animals.

Comparative study on the effect of phosphorylated TCR zeta chain ITAM sequences on early activation events in Jurkat T cells.

One of the main dilemma in T cell receptor (TCR) signal transduction is whether the presence of multiple Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) within the TCR signaling module serves for signal amplification or signal distribution. To contribute to answer this question, we analyzed the effect of synthetic oligopeptides representing the three bi-phosphorylated zeta chain-ITAMs on the early signaling events in permeabilized leukemia T cells. Our main observations were as follows: 1/Stimulation of the cells with the bi-phosphorylated membrane proximal and central ITAMs (zeta (1)y(p)y(p) and zeta (2)y(p)y(p), respectively) resulted in a strong phosphorylation of proteins with a similar pattern. In contrast, the membrane distal ITAM, zeta (3)y(p)y(p) had a reduced ability to promote tyrosine phosphorylation and failed to induce the phosphorylation of a number of proteins. 2/ The phospho-peptide induced tyrosine phosphorylation events were at least partially mediated by p56(lck) and Syk/ZAP70 protein tyrosine kinases as it was shown in p56(lck) and Syk/ZAP70 deficient Jurkat variants. 3/The patterns of the association of the adaptor protein, Grb2 with tyrosine phosphorylated proteins following cell stimulation with the bi-phosphorylated membrane proximal or the central ITAMs were similar, while the membrane distal ITAM was unable to induce any of these associations. Our data provide additional evidence that the three zetaITAMs differ in their capacity to induce tyrosine phosphorylation of intracellular proteins in permeabilized T cells, depending to their primary sequence. The first and second ITAM sequences of the zeta chain may have similar but not totally overlapping functions. This conclusion results from their similar but not identical abilities to induce tyrosine phosphorylation and association of Grb-2 with intracellular phosphoproteins. In contrast, the third ITAM (zeta3) may have distinct functions since this peptide fails to induce tyrosine phosphorylation of a number of proteins compared to the other two ITAMs, and it is unable to induce either new association or the increase in the amount of Grb-2 associated phosphoproteins.

Detection of surgical glove integrity.

Surgical glove integrity is essential for universal precautions; glove safety is verified by the water load test (WLT). Concerns regarding glove injury have prompted newer testing methodologies, including electrical conductance testing (ECT); however, the sensitivities of these tests are not known. We compared the sensitivity of WLT and ECT in detecting glove needle-stick injury in two commonly used brands of surgical gloves. Punctures were made with hollow-bore and solid surgical needles of various configurations. The WLT failed to detect glove holes from the smallest-caliber needles and only detected the injury in 60 per cent for the largest caliber. The ECT provided a graded index of glove injury in all holes made by both solid surgical needles and hollow-bore needles. The WLT is a poor test for clinical defects in latex surgical gloves; the ECT is significantly more sensitive and provides a gauge of the cross-sectional area of the defect. Interbrand differences in self-sealing properties of surgical gloves were evidenced and may be clinically relevant after glove perforation.

Vascular endothelial growth factor expression is independent of hypoxia in human malignant glioma spheroids and tumours.

We recently showed that severe hypoxia was not universally present adjacent to necrosis in human glioma xenografts and spheroids established from the M059K, M006, M006X, M006XLo and M010b cell lines. Using these glioma models, we wished to test whether oxygen serves as a regulator of cellular VEGF expression in situ. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression in sections of glioma xenografts and spheroids in which hypoxic regions and regions with well-oxygenated necrosis were identified on contiguous sections by use of the hypoxia-specific marker, 3H-misonidazole. Independent validation of the presence of radiobiologically hypoxic cells in M006 xenografts was undertaken using the comet assay. Northern blotting analyses of monolayer cells demonstrated significant up-regulation of VEGF mRNA in the M006X line at oxygen concentrations of 6% and below. ISH analysis of VEGF mRNA showed unexpectedly strong staining for VEGF mRNA across the entire viable rim of M006X and M006XLo glioma spheroids. Similarly, in virtually all xenograft tumours of the M059K, M006 and M010b lines, VEGF ISH showed similar staining across all regions of healthy cells up to the border of necrosis. Only in one M006X tumour was there a suggestion of increased VEGF expression in cells adjacent to necrosis. IHC for VEGF showed good concordance with the ISH results. IHC analysis of the VEGF receptor flt-1 showed strong tumour cell staining in M006XLo glioma cells. In human glioma spheroids and xenograft tumours, regions of severe hypoxia do not correspond to areas of up-regulated VEGF expression; in fact, VEGF expression is quite uniform. Furthermore, this and our previous study demonstrate that levels of VEGF expression vary among sublines (M006, M006X and M006XLo) derived from a single human glioma specimen.

Modulation of oxygen consumption rate and vascular endothelial growth factor mRNA expression in human malignant glioma cells by hypoxia.

Cellular responses to hypoxia include modulation of respiration rate and up-regulation of genes which encode for angiogenesis factors. We tested whether human malignant glioma cells vary in their response to hypoxic stress over the range of oxygen concentrations which exist in tumours. In five cell lines tested, decreased oxygen availability resulted in decreased rates of oxygen utilization, however substantial differences in the magnitude of the response were observed. Northern blot analysis was used to study induction of vascular endothelial growth factor mRNA in response to hypoxia. In two cell lines, modest hypoxia increased vascular endothelial growth factor mRNA levels compared with those of aerobic controls. In two additional cell lines, vascular endothelial growth factor mRNA was constitutively expressed under aerobic conditions and was not further increased by hypoxia. These findings demonstrate that differences in the response to hypoxia exist among human malignant glioma cell lines and suggest that therapies designed to exploit tumour hypoxia may have varying effects in tumours with different hypoxic stress responses.

Variable presence of hypoxia in M006 human glioma spheroids and in spheroids and xenografts of clonally derived sublines.

Recently we reported the variable presence of hypoxia adjacent to necrosis in human glioma lines grown as subcutaneous tumours in severe combined immunodeficient (SCID) mice. To assess the basis for this observation, we examined the pattern of oxygenation in M006 and M006XLo glioma spheroids. We found a wide range of binding of [3H]misonidazole to cells adjacent to the necrotic core, analogous to the patterns seen in xenografts, indicating substantial differences in the central oxygen tension of the spheroids. Clonal selection was used to isolate single cell-derived sublines of the M006XLo line. Some sublines gave spheroids that showed narrow distributions of [3H]misonidazole binding to the cells adjacent to necrosis, whereas other sublines showed a range of binding similar to that seen in spheroids of the parent line. After additional passages in monolayer culture, clonal sublines occasionally gave rise to spheroids in which the mean oxygen tension of cells adjacent to necrosis differed substantially from that of the initial spheroids. No relationship was evident between the thickness of the rim of viable cells and the presence or absence of central hypoxia, over a wide range of rim thickness. These results indicate that different oxygenation characteristics of glioma spheroids and tumour microregions are unlikely to arise from stable genetic variants coexisting in the parent line.

Signaling of apoptotic lung injury by lipid hydroperoxides.

BACKGROUND: Acute lung injury is common after shock and sepsis, but the pathophysiology is unclear. Lipid hydroperoxide products including 4-hydroxynonenal (HNE) increase significantly during these insults and may induce apoptosis. This study investigates the role of pathophysiologic concentrations of HNE on isolated lung biophysical function and apoptosis. METHODS: Male Sprague-Dawley rat lungs were isolated and perfused with Krebs-Henseleit buffered solution for 120 minutes. Hydroxynonenal (50 micromol/L) or vehicle was added to the perfusate at 60 minutes. Lung elastance and perfusion pressure were determined. Perfusate glutathione and lactate dehydrogenase were determined at 30-minute intervals. Genomic DNA was extracted for electrophoretic determination of apoptotic laddering. RESULTS: There were no differences in any parameter measured before HNE infusion. Lung edema increased significantly with HNE infusion; a trend increase in lung elastance and perfusion pressure was noted. DNA laddering characteristic of apoptosis was noted in HNE-treated lungs that was absent in control animals. CONCLUSION: Lipid hydroperoxide products formed during shock or sepsis may be causally related to lung injury. Low concentrations of a candidate metabolite, HNE, appear to induce significant lung injury and apoptosis, which may partially mediate lung injury during shock and sepsis.

Calcium blockade reduces renal apoptosis during ischemia reperfusion.

Apoptosis is well described in invertebrates and recently documented in mammals. The prevalence and pathophysiology of mammalian apoptosis is unknown and may have clinical ramifications. The aim of this study is to investigate the apoptotic response during kidney ischemia-reperfusion (I/R) injury. Kidney I/R was initiated in anesthetized rats by occlusion of the renal pedicle for 45 min with or without pretreatment with .2 mg/kg verapamil: control animals received sham exposure. Flow was re-established after ischemia and the animals were allowed to recover for 24 h. Bilateral kidneys were harvested for DNA electrophoresis, Western analysis for p53, Northern analysis for c-myc expression, and light and electron microscopic analysis. Kidney I/R caused characteristic DNA laddering in the clamped kidney, and less extensive laddering was seen in the contralateral kidney. Light and electron microscopic analysis confirmed apoptotic morphology in the reperfused tissues. Verapamil pretreatment completely abolished DNA laddering and attenuated the microscopic evidence of apoptosis. p53 levels were increased by I/R in the ischemic kidney and moderately increased in the contralateral organ. c-myc mRNA levels were increased by the I/R insult. Kidney I/R injury may induce global apoptosis, which seems to be associated with an alteration in calcium homeostasis. The increase in p53 and c-myc mRNA levels seen with I/R may facilitate apoptosis. Calcium modulation seems to reduce apoptosis during I/R and may have therapeutic implications.

Effect of triiodothyronine augmentation on rat lung surfactant phospholipids during sepsis.

Surfactant functional effectiveness is dependent on phospholipid compositional integrity; sepsis decreases this through an undefined mechanism. Sepsis-induced hypothyroidism is commensurate and may be related. This study examines the effect of 3,3',5-triiodo-L-thyronine (T3) supplementation on surfactant composition and function during sepsis. Male Sprague-Dawley rats underwent sham laparotomy (Sham) or cecal ligation and puncture (CLP) with or without T3 supplementation [CLP/T3 (3 ng/h)]. After 6, 12, or 24 h, surfactant was obtained by lavage. Function was assessed by a pulsating bubble surfactometer and in vivo compliance studies. Sepsis produced a decrease in surfactant phosphatidylglycerol and phosphatidic acid, with an increase in lesser surface-active lipids phosphatidylserine and phosphatidylinositol. Phosphatidylcholine content was not significantly changed. Sepsis caused an alteration in the fatty acid composition and an increase in saturation in most phospholipids. Hormonal replacement attenuated these changes. Lung compliance and surfactant adsorption were reduced by sepsis and maintained by T3 treatment. Thyroid hormone may have an active role in lung functional preservation through maintenance of surfactant homeostasis during sepsis.

Effect of thyroid hormone (T3)-responsive changes in surfactant apoproteins on surfactant function during sepsis.

BACKGROUND: Long surfactant phospholipids are altered during sepsis; the role of surfactant apoproteins is unknown. This study investigates the effect of cecal ligation and puncture (CLP) on surfactant functional effectiveness and apoprotein transcriptional activity with or without T3 replacement. METHODS: Male Sprague Dawley rats underwent sham laparotomy or CLP with or without T3 replacement. Lung compliance, surfactant adsorption, and surface tension were measured with a surfactometer. Surfactant apoproteins A, B, and C (SP-A, SP-B, SP-C) mRNA was quantified by Northern blot analysis. RESULTS: Lung compliance was significantly decreased by sepsis; initial surface tension and adsorption values in CLP animals reflected apoprotein dysfunction. Sepsis decreased SP-A mRNA levels and increased SP-B mRNA; SP-C mRNA were unchanged. T3 treatment improved compliance, adsorption, and ST isotherms in septic animals. CONCLUSION: T3 attenuated sepsis-induced surfactant dysfunction and SP-A and SP-B transcriptional changes during sepsis. This suggests an interaction between the thyroid, surfactant apoproteins, and lung surfactant functional effectiveness and requires further study.