Immunoglobulin deficiency as an indicator of disease severity in patients with COVID-19.

Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.

Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS.

Pharmacokinetic interaction of riociguat with ketoconazole, clarithromycin, and midazolam.

Riociguat is a soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension that is principally metabolized via the cytochrome P450 (CYP) pathway. Three studies in healthy males investigated potential pharmacokinetic interactions between riociguat and CYP inhibitors (ketoconazole, clarithromycin, and midazolam). In two studies, subjects were pretreated with either once-daily ketoconazole 400 mg or twice-daily clarithromycin 500 mg for 4 days before cotreatment with either riociguat 0.

Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects.

Background And Objectives: Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of pulmonary arterial hypertension (PAH). Warfarin, an anticoagulant often prescribed to patients with PAH, has a narrow therapeutic index and is prone to potential interactions with drugs. This study assessed the effects of macitentan on the pharmacokinetics and pharmacodynamics of single-dose warfarin in healthy subjects.

ATG induction in renal transplant recipients: Long-term hazard of severe infection is associated with long-term functional T cell impairment but not the ATG-induced CD4 cell decline.

Background And Methods: We showed previously that rabbit ATG induction induces a strong decrease of CD4+ T cells together with impaired in vitro IL-2 secretion up to 1 year post-transplant. To further characterize long-term immunological effects of ATG induction 2 and 5 years post-transplant, we used sensitive intracellular cytokine analysis in the same prospective study of 84 renal transplant recipients (ATG, n=44).

Results: A significantly increased frequency of severe infectious disease (HR=2.

Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

Objective: To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs.

Methods: 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days.

Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long-acting release in healthy volunteers: a single-center Phase I study.

Objective: This study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PKs) of different doses of a long-acting release (LAR) formulation of pasireotide in healthy subjects.

Design: Single-center, open-label, randomized Phase I study.

Methods: Twelve healthy male subjects received a single s.

Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response.

The Symphony study showed superior 1-year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin-secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post-transplant. Tacr- compared with CsA-based immunosuppression was independently associated with increased IL-2 (P<0.

Acetylcholine and chronic vasculopathy in rat renal allografts.

Background: Chronic allograft vasculopathy (CAV) is an important aspect of chronic allograft injury, which limits the long-term success of renal transplantation. The pathogenesis of CAV is ill defined, and no effective therapies exist. Acute rejection episodes are a major risk factor for CAV.

Reduced expression of arrestin beta 2 by graft monocytes during acute rejection of rat kidneys.

During acute rejection, numerous pro-inflammatory and cytotoxic monocytes accumulate in the vasculature of experimental renal allografts. Arrestins (ARRBs) are cellular regulators of inflammation, but nothing is known about their expression during rejection. Intravascular mononuclear graft leukocytes were isolated 4 days after kidney transplantation.

Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys.

During self-limiting acute rejection preceding chronic vasculopathy, large amounts of leukocytes, predominantly monocytes, interact with the endothelium of renal allografts. We aim to characterize them and to identify targets for functional and interventional studies. Leukocytes were harvested by vascular perfusion from Fischer 344 to Lewis renal allografts or Lewis isografts, followed by flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling.

Pharmacokinetics of a new orodispersible tablet formulation of vardenafil: results of three clinical trials.

Background: Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject's mouth without the need for water or other liquids.

Bone marrow transplantation demonstrates medullar origin of CD34+ fibrocytes and ameliorates hepatic fibrosis in Abcb4-/- mice.

Unlabelled: Bone marrow (BM)-derived stem cells and CD34(+) fibrocytes are associated with fibrogenesis in several organs. In an Abcb4(-/-) mouse model for sclerosing cholangitis alpha-smooth muscle actin-positive (alpha-SMA(+)) myofibroblasts are thought to play a pivotal role in hepatic fibrogenesis. The aim of this study was 2-fold: (1) to demonstrate that the origin of an important fibrogenetic cell population is the BM; and (2) to investigate whether transplantation of BM (BM-Tx) affects liver function, staging, and grading.

Induction of lymphocyte apoptosis in a murine model of acute lung injury--modulation by lipid emulsions.

Acute lung injury (ALI) and sepsis are the major causes of mortality in intensive care units. Lymphocytes apoptosis is a hallmark feature of late detrimental sepsis. Parenteral nutrition in critically ill patients is based on lipid emulsions, but the impact of ALI and lipid emulsions on lymphocytes has not been defined.

Neuropeptide Y is expressed by rat mononuclear blood leukocytes and strongly down-regulated during inflammation.

Neuropeptide Y (NPY), a classical sympathetic comediator, regulates immunological functions including T cell activation and migration of blood leukocytes. A NPY-mediated neuroimmune cross-talk is well conceivable in sympathetically innervated tissues. In denervated, e.

Single-dose pharmacokinetics and safety pharmacodynamics of formoterol delivered by two different dry powder inhalers.

The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were recorded.

Fatty acids differentially influence phosphatidylinositol 3-kinase signal transduction in endothelial cells: impact on adhesion and apoptosis.

In contrast to n-6 fatty acids like arachidonic acid (AA), the anti-inflammatory potential of n-3 fatty acids such as docosahexaenoic acid (DHA) has been demonstrated. We examined the phosphatidylinositol (PI)3-kinase dependent effects of AA versus DHA on monocyte rolling, adhesion and transmigration through inflammatory activated human umbilical venous endothelial cells (HUVEC) as well as on apoptosis, to investigate the impact on vascular inflammation. HUVEC were pre-incubated with AA, DHA or sham, and stimulated with VEGF, TNF-alpha or staurosporine.

Acute rejection of experimental lung allografts: characterization of intravascular mononuclear leukocytes.

Leukocytes interacting with endothelia of lung allografts probably play a seminal role in acute rejection, but have not been characterized before. Transplantation was performed in the Lewis to Lewis and in the Dark Agouti to Lewis rat strain combinations. DNA replication was detected in T-cells on day 2 after pulse-labelling in vivo with 5-bromo-2'-deoxyuridine (BrdU).

ATG induction therapy: long-term effects on Th1 but not on Th2 responses.

Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses.