Indinavir Sulfate Renal Toxicity in a Pediatric Hemophiliac with HIV Infection

1997 ◽  
Vol 31 (10) ◽  
pp. 1146-1149 ◽  
Author(s):  
David P Ascher ◽  
Mitchell D Lucy
Keyword(s):  
Hiv Infection ◽  
Renal Toxicity ◽  
Nasal Congestion ◽  
Elevated Serum ◽  
Coagulation Factor ◽  
Low Grade ◽  
Cefpodoxime Proxetil ◽  
Case Summary ◽  
Indinavir Sulfate ◽  
Sterile Pyuria

OBJECTIVE: To report a case of renal toxicity associated with administration of indinavir sulfate in a pediatric hemophiliac with HIV infection. CASE SUMMARY: A 16-year-old white hemophiliac boy with HIV infection secondary to tainted coagulation factor VIII was treated with indinavir sulfate. The patient developed gross hematuria, proteinuria, pyuria, abdominal pain, increased bilirubin, an elevated serum creatinine (SCr) of 1.2 mg/dL (baseline 0.9–1.0), and symptoms of renal colic within 1 month of starting indinavir sulfate therapy. Approximately 2 months later the patient developed a low-grade fever with a further increase in SCr. He was prescribed a 10-day course of cefpodoxime proxetil for a possible urinary tract infection. One week later, the patient developed fever, chills, nausea, vomiting, decreased appetite, sterile pyuria, nasal congestion, and an elevated SCr of 1.3–1.7 mg/dL. Indinavir sulfate and cefpodoxime proxetil were discontinued and the patient was suspected of having tubulointerstitial nephritis secondary to indinavir sulfate. The patient's nephritis resolved and the SCr decreased to 1.1 mg/dL within 1 month of discontinuing indinavir sulfate. CONCLUSIONS: This case demonstrates the potential for renal toxicity with the use of indinavir sulfate in HIV-infected hemophiliacs.

scholarly journals Serum Chemerin Levels Vary with Time of Day and Are Modified by Obesity and Tumor Necrosis Factor-α

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2590-2602 ◽  
Author(s):  
Sebastian D. Parlee ◽  
Matthew C. Ernst ◽  
Shanmugam Muruganandan ◽  
Christopher J. Sinal ◽  
Kerry B. Goralski
Keyword(s):  
Leptin Receptor ◽  
Elevated Serum ◽  
Time Of Day ◽  
Obese Mouse ◽  
Protein Synthesis Inhibitor ◽  
Low Grade ◽  
Rhythmic Pattern ◽  
Oscillatory Pattern ◽  
Primary Mouse

Chemerin is an adipokine with important regulatory roles in adipogenesis. In humans, serum total chemerin (i.e. prochemerin plus chemerin) levels are positively associated with body mass index and metabolic syndrome. However, the mechanisms that increase serum chemerin concentration are unknown. We hypothesized that chronic low-grade inflammation that occurs in obesity promotes chemerin production by adipocytes. Consistent with this, TNFα treatment of 3T3-L1 adipocytes increased bioactive chemerin levels in the cell media as detected using a CMKLR1 cell-based bioassay. This effect was blocked by the protein synthesis inhibitor cycloheximide and protein secretion inhibitor brefeldin A, indicating that TNFα may enhance prochemerin synthesis and secretion from adipocytes. In vivo, TNFα produced a time-dependent increase in serum total chemerin and bioactive chemerin. Bioactive chemerin was produced by primary mouse adipocytes and hepatocytes. Only primary adipocyte-derived chemerin was responsive to TNFα regulation implicating adipocytes as a potential source of elevated serum chemerin after TNFα exposure in vivo. In lean mice, serum total chemerin levels oscillated with peak levels occurring during daytime and trough levels at night. Comparatively, leptin- and leptin receptor-deficient obese mice, which have elevated adipose tissue expression of TNFα, displayed elevated serum total chemerin levels with an enhanced oscillatory pattern. In summary, our novel results identified TNFα as a positive regulator of adipocyte-derived chemerin. We corroborate the finding of elevated chemerin in obese humans by identifying elevated serum levels of total chemerin in two obese mouse models with a corresponding alteration in the rhythmic pattern of serum chemerin levels.

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

2003 ◽  
Vol 95 (4) ◽  
pp. 1656-1663 ◽  
Author(s):  
C. A. Rivera ◽  
M. H. Tcharmtchi ◽  
L. Mendoza ◽  
C. W. Smith
Keyword(s):  
Acute Phase ◽  
Hepatic Injury ◽  
Acute Phase Proteins ◽  
Elevated Serum ◽  
Hindlimb Unloading ◽  
Low Grade ◽  
Systemic Blood ◽  
Blood Samples ◽  
Amyloid A ◽  
Organ Systems

Hindlimb unloading (HU) is known to induce physiological alterations in various organ systems that mimic some responses observed after exposure to microgravity. In the present study, the effects of up to 4 wk of HU on the liver were assessed in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator of hepatic injury, were measured in portal and systemic blood samples. Endotoxin was elevated by ∼50% in portal blood samples of mice and rats but was not detectable in systemic blood. This low-grade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice as indicated by inflammation and elevated serum transaminase activities. Blood levels of the cytokine TNF-α were increased by ∼50% in C57BL/6 mice; no significant elevation of this cytokine was detected in rats. Messenger RNA levels of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide binding protein were significantly enhanced after 3 wk of HU in endotoxin-sensitive rodents. In contrast, no histological changes or significant increases in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal endotoxin levels of 222 ± 83.4 pg/ml. At the 3-wk time point, expression of acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after 4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these findings indicate that HU induced mild portal endotoxemia, which contributed to the observed hepatic injury in endotoxin-sensitive rodents.

scholarly journals The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection

2022 ◽  
Author(s):  
Nadia Anikeeva ◽  
Maria Steblyanko ◽  
Leticia Kuri-Cervantes ◽  
Marcus Buggert ◽  
Michael R Betts ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Lipid Bilayers ◽  
Cd8 T Cells ◽  
Premature Aging ◽  
Low Grade ◽  
Naive T Cells ◽  
Infected People ◽  
Naïve T Cells ◽  
Chronic Hiv Infection

It is well-established that chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system in HIV patient including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from chronically HIV infected people, we have analyzed cellular morphology and dynamics of the synaptic interface followed exposure of peripheral polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers. The above parameters were linked to pattern of degranulation that determines efficiency of CD8 T cells cytolytic response. We found a large fraction of naive T cells from HIV infected people developing mature synapses and demonstrating focused degranulation, a signature of a differentiated T cells. Further differentiation of aberrant naive T cells leads to development of anomalous effector T cells undermining their capacity to control HIV and other viruses that could be contained otherwise.

scholarly journals Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Flora Mikaeloff ◽  
Sara Svensson Akusjärvi ◽  
George Mondinde Ikomey ◽  
Shuba Krishnan ◽  
Maike Sperk ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Cell Model ◽  
Antiretroviral Drugs ◽  
Metabolic Reprogramming ◽  
System Level ◽  
People Living With Hiv ◽  
Low Grade ◽  
Middle Income ◽  
Living With Hiv

AbstractDespite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.

Respiratory syncytial viral infection in infants: nursing implications

1990 ◽  
Vol 10 (2) ◽  
pp. 74-79 ◽  
Author(s):  
DA Adams ◽  
EA McFadden
Keyword(s):  
Viral Infection ◽  
Nasal Congestion ◽  
Clinical Status ◽  
Respiratory Acidosis ◽  
Low Grade ◽  
Presenting Symptoms ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Tract Disease ◽  
Respiratory Syncytial Viral Infection

Respiratory syncytial viral infection is the leading cause of acute lower respiratory tract disease in infants and young children. Presenting symptoms include rhinorrhea, nasal congestion, a low grade fever, and a cough. Hypoxemia and respiratory acidosis are the most common presentation for infants requiring intensive care. Critical care nurses must skillfully assess the infant's clinical status and response to medical treatment, implement and enforce isolation procedures, and remain sensitive to the emotional and psychologic needs of RSV-infected infants and their families. They must be knowledgeable regarding the latest research and recommendations concerning isolation policies and safe administration of ribavirin therapy in order to maximize the care for infants experiencing acute respiratory distress caused by RSV infection.

scholarly journals Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats

2017 ◽  
Vol 313 (2) ◽  
pp. E107-E120 ◽  
Author(s):  
Mathilde Guerville ◽  
Anaïs Leroy ◽  
Annaëlle Sinquin ◽  
Fabienne Laugerette ◽  
Marie-Caroline Michalski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Elevated Serum ◽  
Caloric Intake ◽  
Western Diet ◽  
Chow Diet ◽  
Low Grade ◽  
Mrna Levels ◽  
Intestinal Alkaline Phosphatase ◽  
Ad Libitum ◽  
Metabolic Endotoxemia

Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -β gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.

scholarly journals High-Sensitivity C-Reactive Protein and Carotid Intima Media Thickness as Markers of Subclinical Inflammation and Atherosclerosis in Pediatric Patients with Hypercholesterolemia

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5118
Author(s):  
Lana Blinc ◽  
Matej Mlinaric ◽  
Tadej Battelino ◽  
Urh Groselj
Keyword(s):  
Subclinical Atherosclerosis ◽  
Elevated Serum ◽  
High Sensitivity ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Low Grade ◽  
C Reactive Protein ◽  
Atherosclerosis Progression ◽  
Reactive Protein ◽  
Media Thickness

Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in one of the causative genes (LDLR, APOB, PCSK9). In polygenic hypercholesterolemia (PH), the disease-causing genetic variant is absent; it is likely the cumulative result of multiple single nucleotide polymorphisms in LDL metabolism-related genes and other factors, such as lifestyle and environment. In high risk groups, such as patients with FH, an effective primary prevention of CVD must begin in childhood. High-sensitivity C-reactive protein (hsCRP) and carotid intima media thickness (cIMT) are two potential minimally invasive correlates of inflammation and subclinical atherosclerosis progression. hsCRP and cIMT have been shown to be significantly increased in patients with FH and PH relative to healthy controls, with some studies yielding conflicting results. In this review, we aim to summarize current knowledge and recent findings regarding the applicability of hsCRP and cIMT as markers of low-grade inflammation and subclinical atherosclerosis, focusing especially on children and adolescents with hypercholesterolemia.

Low-Grade Inflammation in Hemophilia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1115-1115
Author(s):  
Lynn M Knowles ◽  
Hermann Eichler ◽  
Jan Pilch
Keyword(s):  
Adipose Tissue ◽  
Blood Circulation ◽  
Prophylactic Treatment ◽  
Coagulation Factor ◽  
Low Grade ◽  
Adipose Tissue Inflammation ◽  
C Reactive Protein ◽  
Tissue Inflammation ◽  
Reactive Protein ◽  
Low Grade Inflammation

We previously showed that impaired clotting in hemophilia leads to a deficit in macrophage differentiation, which negatively affects critical regenerative macrophage functions such as clot infiltration and red blood cell phagocytosis. These data provide a functional basis for the delayed wound healing as well as protracted joint inflammation commonly observed in hemophiliacs and suggest that altered macrophage function is linked to the activation of the innate immune system. We, therefore, hypothesize that hemophiliacs suffer from chronic low-grade inflammation, which in turn can affect joint health, tissue regeneration and age-related ailments such as cardiovascular disease. For this study, we collected citrated blood from 48 adult male patients with hemophilia A or B with an average age of 36 years and a body mass index (BMI) of 27.7 kg/m2. The majority of patients had a residual FVIII/FIX activity < 1% (77%) and received prophylactic treatment (60%) with a recombinant or plasmatic coagulation factor concentrate. Approximately one-half of the patients had target joints or other bleeding events in the last 3 months and one-third of the patients had contracted HBV, HCV or HIV. For controls, we randomly recruited male blood donors (n = 60; age, 35.8 years; BMI, 27.0) from our blood donation center. To assess inflammation in hemophiliacs, we analyzed platelet-poor plasma from our main collective and a BMI-adjusted cohort using commercially available ELISA kits. The results showed a significant increase of two acute-phase proteins, C-reactive protein and leptin in hemophilia patients compared to healthy controls. Further analysis demonstrated that C-reactive protein and leptin expression inversely correlated with the residual clotting activity as both parameters were high in patients with severe Hemophilia A or B and comparatively low in patients with moderate to mild hemophilia. Of note, there was neither an increase of C-reactive protein or leptin in hemophilia patients with recent bleeding (< 3 month), arthropathy, chronic viral infection nor a decrease in patients with coagulation factor activity > 10% due to prophylactic treatment or recent replacement. Therefore, these data suggest a basic link between clotting deficiencies and chronic low-grade inflammation. Low-grade inflammation is maintained by adipokines, which originate from the adipose tissue and are modulated by a process known as adipose tissue inflammation. In addition to the upregulation of the pro-inflammatory leptin, we detected a significant down-regulation of the anti-inflammatory adiponectin in the plasma of hemophilia patients resulting in a markedly decreased adiponectin/leptin ratio. To enquire if the adipose tissue inflammation in hemophilia originates from gram-negative gut bacteria that translocate into the blood circulation, we also detected elevated plasma levels of lipopolysaccharide-binding protein and hepcidin in hemophilia patients. Together, these data support the concept that low-grade inflammation in hemophilia originates from lipopolysaccharide, which in turn causes adipose tissue inflammation. To test the hypothesis that low-grade inflammation in hemophilia is caused by decreased clotting activity, we collected blood from hemophilia B patients before and after transition from a conventional standard-half-life factor IX concentrate to a prophylactic therapy with an elongated half-life (EHL) FIX (Albutrepennonacog alfa, Idelvion®). Following up on the enhanced factor replacement after > 6 months, we observed a return of hepcidin plasma levels back to baseline values in healthy controls. The decreased hepcidin values from EHL FXI therapy correlated with healing of target joints suggesting that EHL FIX not only controls bleeding but also inflammation. Together, our data demonstrate a specific link between hemophilia and low-grade inflammation that appears to involve increased lipopolysaccharide levels in the blood circulation and subsequent adipose tissue inflammation. In addition, we present evidence that low-grade inflammation is the result of the underlying clotting deficit and that sustained normalization of the clotting deficit with EHL factors ameliorates inflammation. Disclosures Eichler: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Pilch:CSL Behring: Other: Grants (investigator initiated), Speakers Bureau; ASPIRE Award/Pfizer: Other: Grants (investigator initiated); Bayer: Consultancy, Speakers Bureau; Roche: Consultancy.

Increased Risk for Thromboembolism Associated with High Coagulation Factor VIII (F VIII) Levels in Patients with Malignant Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1380-1380
Author(s):  
Martin Mohren ◽  
Ilka Markmann ◽  
Astrid Franke ◽  
Kathleen Jentsch-Ullrich ◽  
Michael Koenigsmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Malignant Lymphoma ◽  
Solid Tumors ◽  
Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Hematologic Malignancies ◽  
Low Grade ◽  
Factor V Leiden Mutation ◽  
Increased Risk

Abstract An increased annual incidence of thromboembolic events (TE) of up to 11% has been observed in patients with solid tumors, whereas there exists little data on TE in hematologic malignancies. A previous study found a 6,6% incidence of TE in patients with high grade Non Hodgkin’s lymphoma (HG-NHL) mostly occuring during the first three months of therapy. Little is known about pathogenesis and risk factors in this patient group. We retrospectively evaluated the medical records of all patients with malignant lymphoma treated at our institution between 1991 and 2004. In a seperate effort laboratory analysis for detection of acquired and hereditary thrombophilia was performed at diagnosis and during treatment in 44 patients with various hematologic malignancies: HG-NHL (n = 22), Low grade- NHL (LG-NHL) (n = 7), Hodgkin’s disease (HD) (n = 6), CNS-lymphoma (n = 1) and acute myeloid leukemia (AML) (n = 8). A total of 96 TE occurred in 80 of 1048 patients (7,6%) with malignant lymphoma: DVT (n = 51), pulmonary embolism (n = 19), central venous catheter thrombosis (n = 11), upper extremity thrombosis due to tumor compression (n = 9), central nervous system thrombosis (n = 3), arterial thrombosis (n = 2) and portal vein thrombosis (n = 1). 69 TE (72%) occurred during treatment, whereas 27 (28%) were diagnosed prior to (n = 16) (17%) or after completion of therapy (n = 11) (11%). 9 patients (9%) had comorbid solid tumors. In 12 patients (15%) results of thrombophilia screening were available and FVIII levels were high (&gt; 150%) in 7 (58%). In the prospectively analyzed patient cohort 30 (68%) had high FVIII levels, 22 (50%) showing very high levels (&gt; 180%). High FVIII was associated with high von Willebrand factor (vWF) and increased collagen binding activity, but not with elevated IL 6 or TNF-a. 4 patients (9%) had heterozygous factor V Leiden mutation, one had the G20210A mutation of the prothrombin gene. Fibrinolysis was normal in all patients as were protein C, S and AT-III. No anticardiolipin antibodies or lupus anticoagulants were detected. However only 2 patients (4,4%) in this cohort developed TE, one of whom also had heterozygous protein C resistance. Patients with malignant lymphoma are at substantial risk for TE, especially during treatment, thus prophylactic anticoagulation seems warranted. Our study shows sustained strikingly high factor VIII levels in patients with malignant lymphoma even months or years after a TE as well as in a prospectively analyzed, yet mostly asymptomatic cohort with lymphoma and acute leukemia. Infection as a cause of secondary F VIII elevation in these patients was ruled out by absence of fever and normal IL 6 and TNF-a. Increased FVIII activity (&gt; 150%) has been recognized as an independent risk factor for TE, however the pathogenesis is unclear so far and high FVIII and vWF levels have previously also been found in Multiple Myeloma patients. Ongoing investigations will focus on the implication of these findings in the pathophysiology of hematologic disease.

Primary Oral Cavity Lymphomas. Features of 29 Patients Assisted at Oncology Hospital Marie Curie, Buenos Aires Argentina.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4617-4617
Author(s):  
Marta O. Dragosky ◽  
Nelly Frascino ◽  
Susana Alcaraz ◽  
Isabel Annetta ◽  
Laura Devoto ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Hiv Infection ◽  
International Prognostic Index ◽  
Cell Lineage ◽  
Prognostic Index ◽  
Low Grade ◽  
High Grade ◽  
Male Predominance ◽  
Prognostic Assessment ◽  
Oral Malignancies

Abstract Primary oral cavity lymphomas (POCV) are uncommon and must be distinguish from widespread involvement of systemic lymphomas. Countries with high incidence of oral malignancies report cancer predominance. HIV+ population have higher prevalence than immunocompetent patientes. Alcohol and tobacco have been mentioned like risk factors. The International Prognostic Index has been taken in consideration. Patients attended Hospital on referal from medical or odontology centers and others on their own. A total of 29 patientes were studied. Aged 21 to 70, media 47,3 years. Male predominance: 69%. Histopathology: NHL high grade B: 19 cases, NHL low grade B: 4, NHL high grade T: 3 and plasmoblastic 3. Sites: superior maxilla: 12, inferior maxilla 11, tongue 3, palate 3. No predominance for right or left locations. HIV+ 9 patients (31%) The prevalence among inmmunocompetent was markedly lower: in 662 diagnosed with NHL 20 cases=3,02%, in 32 NHL HIV+ 9 cases= 28,12%. More frequent complaints were: painless swell of the maxilla, movable teeth, dysphagia, facial edema. The stages were I and II, 28% with locoregional extension: adenopathies or bone infiltration. The IPI was 0 in17, 1 in 10 and 2 in 2 patients. All patients received chemotherapy (CVP, CHOP), with initial good response and early relapse in HIV+. Conclusions: In correspondence with others reports, we found predominance in male and middle age, B cell lineage and connection with HIV infection. POCL may lead to the diagnosis of an up to then unknown HIV infection. The little specificity of the initial symptons tends to delay the diagnosis and the referal to a specialized center. IPI didn’t prove useful as a prognostic assessment.

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