The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.
View Article and Find Full Text PDFIntroduction: The aim of this study is to evaluate the difference in perioperative complication rate in total hip, bipolar hemiarthroplasties and total knee arthroplasty in patients with Parkinson disease in trauma and elective surgery in our Musculoskeletal Center during a period of 10 years.
Material And Method: Between 2006 and 2016, 45 bipolar hemiarthroplasties in trauma surgery, 15 total knee and 19 total hip arthroplasties in patients with Parkinson's disease were performed. We divided the patients in two groups.
Background: Irrigation and debridement (I&D) is performed for early management of periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). Symptom reporting is a subjective measure and may miss direct management of PJI. Utilizing an objective time interval from index procedure to I&D may better inform treatment decisions.
View Article and Find Full Text PDFThe aim of the study was to examine the frequencies of the genotypes and alleles of ACE insertion/deletion (I/D) polymorphism and their association with dental caries in a sample of Polish children. The study subjects were 120 children with dental caries experience (cases) and 41 caries-free individuals (controls). The genotyping was performed using polymerase chain reaction.
View Article and Find Full Text PDFImportance: There is currently no data detailing the degree to which dermatologists follow CDC/Infectious Diseases Society of America (IDSA) guidelines in the treatment of abscesses, which recommend that incision and drainage (I+D) as primary therapy for skin and soft tissue infections (SSTI).
Objective: To evaluate the management of skin abscesses by dermatologists.
Design, Setting, Participants: A national email survey of 780 dermatologists was conducted from May-June 2012.
Background: It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org 26576 was investigated with a translational approach including preclinical and clinical testing.
View Article and Find Full Text PDFBackground: Type 2 diabetes mellitus is an increasing problem in developed countries. Microvascular diabetic complications can lead to worsening of the quality of life and lifespan shortening of diabetic patients. The renin-angiotensin system (RAS) seems to play an important role in microvascular blood flow.
View Article and Find Full Text PDFUnlabelled: Type 2 diabetes mellitus and arterial hypertension coexist very frequently. About 80% patients with type 2 diabetes suffer for hypertension, which is connected with higher morbidity and mortality from cardiovascular diseases. There are evidences that activation of the renin-angiotensin system (RAS), one of the most potent factors in blood pressure regulation, can decrease insulin sensitivity of tissues.
View Article and Find Full Text PDFObjective: Cholinergic therapy is used in mild-to-moderate Alzheimer's disease (AD) and antiglutamatergic therapy in moderate-to-severe AD. Global scales, as commonly used in clinical trials, blur specifics of disease progression and drug effects. The objective was to assess combination therapy of rivastigmine plus memantine by specific neuropsychological tests in patients with mild-to-moderate AD.
View Article and Find Full Text PDFIntroduction: Left ventricular hypertrophy (LVH) is a well known risk factor of death from cardiovascular causes. Patients with type 2 diabetes mellitus are at particularly high risk of developing cardiovascular disease, which accounts for 80% of deaths in this group. Type 2 diabetes mellitus is probably related to increased left ventricular mass (LVM).
View Article and Find Full Text PDFInsulinresistance is a component of the metabolic syndrome and important pathogenetic factor of type 2 diabetes mellitus. There are evidences that activation of the renin-angiotensin system (RAS) can decrease insulin sensitivity of tissues. As I/D polymorphism of angiotensin converting enzyme (ACE) gene can influence the activity of RAS, it may also influence insulin resistance.
View Article and Find Full Text PDFAMP-activated protein kinase (AMPK) is a key sensor and regulator of intracellular and whole-body energy metabolism. We have identified a thienopyridone family of AMPK activators. A-769662 directly stimulated partially purified rat liver AMPK (EC50 = 0.
View Article and Find Full Text PDFBackground: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD).
Methods: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conner's Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed.
Background: The aim of the study was to verify the hypothesis if the interaction between the G protein beta3 subunit (GNB3) C825T polymorphism and ACE I/D polymorphism could lead to the disclosure of increased activity of sodium-proton exchanger and hypertension.
Methods: The study included 44 male patients, median age: 40 years. Patients were divided into two groups: 26 patients with essential hypertension (EH), and 18 subjects in the normotensive group (C).
Pediatr Infect Dis J
December 2000
An investigator-blinded, randomized, multicenter study was conducted to compare the efficacy and safety of cefdinir and amoxicillin/ clavulanate (amoxicillin/CA) in the treatment of pediatric patients with acute suppurative otitis media. Patients 6 months to 12 years of age were randomized in a 1:1:1 ratio to receive cefdinir 14 mg/kg once-daily, cefdinir 7 mg/kg b.i.
View Article and Find Full Text PDFEur J Gastroenterol Hepatol
January 2000
Background And Aims: Low bone density with an increased risk of vertebral fractures is a frequent complication in inflammatory bowel disease. Since the aetiology of osteopathia in these patients is different compared to postmenopausal or steroid-induced osteoporosis, no treatment strategy is established. Supplementation of calcium and vitamin D has been shown to prevent further bone loss, but no data are available showing the anabolic effect of sodium fluoride in Crohn's disease.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
March 1997
An investigator-blinded, randomized, multicenter study was conducted to compare the efficacy and safety of cefdinir and amoxicillin/clavulanate (amoxicillin/CA) in the treatment of pediatric patients with acute suppurative otitis media. Patients 6 months to 12 years of age were randomized in a 1:1:1 ratio to receive cefdinir 14 mg/kg once-daily, cefdinir 7 mg/kg b.i.
View Article and Find Full Text PDFJ Steroid Biochem
March 1990
We investigated effects of 9-ene-tetrahydrocannabinol (THC) on endocrine and immunological function. Seventeen male volunteers entered into a double blind, randomized study to receive oral THC (10 mg t.i.
View Article and Find Full Text PDFJ Clin Gastroenterol
June 1986
A randomized, double-blind, placebo-controlled study was conducted to determine if concomitant administration of ranitidine, an H2-receptor antagonist, could reduce the gastroduodenal mucosal damage associated with short-term (3 day) aspirin therapy. Nineteen subjects received ranitidine 150 mg b.i.
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