First clinical test of an in vivo CRISPR candidate shows deep protein knockout potential

Abstract Current standards for testing cemented femoral hip stems involve potting the distal third of the stem and applying a cyclic load, see ISO 7206-8. 1995(E). However, this procedure does not test implants for the most prevalent mode of failure — loosening of the prosthesis from the host bone (Malchau et al., 1993). To quantify the expected longevity of implants in a pre-clinical test, a protocol that establishes the rate of loosening of a prosthesis must be developed. Using Radiostercophotogrammetry (RSA), Karrholm et al. (1994) have correlated migration of more than 1 mm within two years of implantation with early loosening of the implant. Therefore, by quantifying the migration of a prosthesis in a laboratory test for the equivalent of two years post implantation, its risk of loosening in vivo can be assessed. In the past, the motion of cemented implants in one direction has been quantified (Manley et al., 1987); whilst other researchers have performed a more complete analysis of the motion of prostheses, but for a limited number of loading cycles (e.g. Schneider et al., 1989). In most of these studies, prosthesis insertions were performed by surgeons. Not only does this introduce subjectivity into the pre-clinical test, but in the case of cemented replacements, variations in stem orientation and cementing pressures will occur. This paper presents the design and initial validation of procedures which may be used for pre-clinical testing of cemented hip stems.

Download Full-text

Urinary Prothrombin Fragment 1+2 in relation to Development of Non-Symptomatic and Symptomatic Venous Thromboembolic Events following Total Knee Replacement

Thrombosis ◽

10.1155/2011/150750 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6

Author(s):

Lars C. Borris ◽

Morten Breindahl ◽

Michael R. Lassen ◽

Ákos F. Pap

Keyword(s):

Total Knee Replacement ◽

Knee Replacement ◽

Operative Procedure ◽

Clinical Test ◽

Prothrombin Fragment ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Patients At Risk ◽

Total Knee

Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of coagulation status after an operative procedure. This study compared uF1+2 levels in patients with symptomatic and non-symptomatic venous thromboembolism (VTE) after total knee replacement (TKR) and in event-free sex- and age-matched controls. Significantly higher median uF1+2 levels were seen in the VTE patients on days 1, 3, and the day of venography (mostly day 7) after TKR compared with controls. The uF1+2 levels tended to be high in some patients with symptomatic VTE; however, the discriminatory efficacy of the test could not be evaluated. In conclusion, this study showed that patients with VTE tend to have significantly higher uF1+2 levels compared with patients without events between days 1 and 7 after TKR surgery. Measurement of uF1+2 could provide a simple, non-invasive clinical test to identify patients at risk of VTE.

Download Full-text

HIV-1 Tropism Evolution after Short-Term Maraviroc Monotherapy in HIV-1-Infected Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00507-12 ◽

2012 ◽

Vol 56 (7) ◽

pp. 3981-3983 ◽

Cited By ~ 6

Author(s):

Alejandro Gonzalez-Serna ◽

María Concepción Romero-Sánchez ◽

Sara Ferrando-Martinez ◽

Miguel Genebat ◽

Francesc Vidal ◽

...

Keyword(s):

Virological Response ◽

Ccr5 Antagonist ◽

Clinical Test ◽

Short Term ◽

Viral Tropism ◽

Viral Loads ◽

Hiv Rna ◽

Hiv 1 ◽

Shed Light

ABSTRACTWe analyzed the evolution of viral tropism after 8 days of maraviroc monotherapy, i.e., we used the maraviroc clinical test (MCT), in 21 patients with and 14 without virological response to the drug (MCT+and MCT−patients, respectively). No increases in CXCR4 inferred viral loads (X4IVLs) were observed in MCT+patients, while X4IVLs increased only in MCT−patients, with X4IVLs of >2 log10HIV RNA copies/ml. These results shed light on the evolution of viral tropism under a CCR5 antagonistin vivo.

Download Full-text

BIOLOGICAL ACTIVITY OF Guazuma ulmifolia Lamark.- SYSTEMATIC REVIEW

DESAFIOS Revista Interdisciplinar da Universidade Federal do Tocantins ◽

10.20873/uftv6-6006 ◽

2019 ◽

Vol 6 (3) ◽

pp. 54-65

Author(s):

Elga Lopes Cunha ◽

Simone Santos Oliveira Barros ◽

Michele Cezimbra Perim ◽

Klismam Marques dos Santos ◽

Maria Laura Martins ◽

...

Keyword(s):

Systematic Review ◽

Experimental Studies ◽

In Vivo Studies ◽

Clinical Test ◽

Pharmacological Effects ◽

Endemic Plant ◽

Toxicological Effects ◽

Guazuma Ulmifolia ◽

Different Parts

ABSTRACT The Guazuma ulmifolia Lamark (Malvaceae) is a non-endemic plant, popularly known as mutamba. Its leaves and roots are used in home remedies against dysentery and diarrhea, in the treatment of prostate, as a uterine stimulant and other diseases. Due to the characteristics presented and the growing interest in this species, a systematic review was carried out on the possible pharmacological and toxicological effects of Guazuma ulmifolia Lamark. As active compounds, the articles cited the presence of flavonoids, saponins, alkaloids, tannins, phenolic compounds and steroids in different parts of the plant and extracted with different solvents. Regarding the experimental studies, no articles were found with clinical test, and only 4 in vivo studies. About the pharmacological effects we can mention activity against leishmaniasis, hypoglycemic, anti-inflammatory, anticholinesterase, anti-obesity, antiseptic, cicatrizant and anthelmintic. The registered toxicological tests were directed against lineages of cancer cells, proving effective, however, there is a need for studies to attest the safety of G. ulmifolia use by the population. Therefore, it is imperative to carry out further studies to ensure the use of this plant, to know doses and form of indication, as well as clinical studies in order to guarantee a correct therapy. Keywords: Guazuma ulmifolia, toxicity, medicinal plants.

Download Full-text

PENAMBATAN MOLEKUL GLUTATION FAUNA LAUT TERHADAP RESEPTOR DARI BEBERAPA PENYAKIT VIRUS

JURNAL PESISIR DAN LAUT TROPIS ◽

10.35800/jplt.9.2.2021.34853 ◽

2021 ◽

Vol 9 (2) ◽

pp. 53

Author(s):

Q Xaxa Alvin Kai ◽

Inneke FM Rumengan ◽

Rosita AJ Lintang ◽

Stenly Wullur ◽

Deiske A Sumilat ◽

...

Keyword(s):

Hepatitis B ◽

Gibbs Energy ◽

Antiviral Drug ◽

Bond Distance ◽

Viral Diseases ◽

Clinical Test ◽

Marine Fauna ◽

Antiviral Compound

Glutathion is a tripeptides produced by almost all living creatures, including marine fauna such as rotifers and shrimps. Judging from the important molecular role of glutathion in living cell, the ability of glutathion as antiviral compound, has been assed by application of the AutodockTools to predict the ability of glutathion as ligand to bind receptors of several viral diseases such as covid-19, malaria, and hepatitis B. Docking results of glutathion toward target receptor were shown by the parameter, Gibbs energy value, and supported by other data such as the amount of hidrogen bond, amino acid residues, and bond distance. Evidently, the glutathion could bind to each receptor of covid-19, malaria and hepatitis B, with values of Gibbs energy (∆G), -7,9, 7,1 and -7,1 kcal/mol, respectively. This proves that glutathion has ability to bind covid-19 receptor, even stronger than its ability to bind receptors of other viral diseases, and to the remdesevir. Between glutathion and covid-19 receptor, there were 11 hidrogen bonds, with distance ranged from 2,76 to 3,25 Å. These were stronger than those between glutathion and receptors of malaria and hepatitis B, only 8 and 4 Å hidrogen bonds, respectively. To develop glutathion as antiviral drug, it is necessary to carry out in vitro and in vivo analyses, prior to clinical test. Therefore, it requires to explore the marine fauna species that produce glutathion and their cultivation.Keywords: molecular docking, glutathion, marine fauna, autodock vina, viral diseases, binding affinity

Download Full-text

THE MANNER OF REMOVAL OF PROTEINS FROM NORMAL JOINTS

Journal of Experimental Medicine ◽

10.1084/jem.57.3.419 ◽

1933 ◽

Vol 57 (3) ◽

pp. 419-433 ◽

Cited By ~ 36

Author(s):

Walter Bauer ◽

Charles L. Short ◽

Granville A. Bennett

Keyword(s):

Horse Serum ◽

Molecular Size ◽

Blood Stream ◽

Great Difficulty ◽

Egg White ◽

Thoracic Duct Lymph ◽

Clinical Test ◽

Serum Globulin ◽

In Vivo Experiments

1. Data are presented showing that precipitin tests can be used for the detection of the proteins contained in egg white and horse serum in the blood stream and thoracic duct lymph following injection into the knee joints of normal dogs. The sera of rabbits immunized against the particular protein employed were used in doing the precipitin tests. 2. Egg white is removed only by way of the lymphatics, appearing more rapidly if the leg muscles are massaged. The removal is even greater from passively exercised joints. 3. Horse serum albumin is readily removed from a normal dog's knee joint by way of the lymphatics alone and with greater rapidity from a passively exercised joint. Horse serum globulin escapes from normal joints with great difficulty, if at all, and therefore does not readily gain entrance into the underlying lymphatic capillaries. 4. The molecular size of a protein readily gaining egress from a joint through the lymphatics is thus defined. 5. The relative sizes of the albumin and globulin molecules contained in horse serum are confirmed by in vivo experiments. 6. The lymphatic system is the essential apparatus for the removal of protein from joints, and any interference with this drainage should promote the formation of intraarticular effusion. The data presented suggest that a simple clinical test for determining the efficiency of the lymphatics draining a single joint can be devised.

Download Full-text

Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract through Transcriptome Profiling

Genes ◽

10.3390/genes11020230 ◽

2020 ◽

Vol 11 (2) ◽

pp. 230 ◽

Cited By ~ 1

Author(s):

Won Kyong Cho ◽

Hye-In Kim ◽

Soo-Yun Kim ◽

Hyo Hyun Seo ◽

Jihyeok Song ◽

...

Keyword(s):

Callus Culture ◽

Developmental Process ◽

Transcriptome Profiling ◽

Clinical Test ◽

Skin Thickness ◽

Aging Effects ◽

Vitro Assay ◽

Culture Extract

Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.

Download Full-text

An effective zinc phthalocyanine derivative against multidrug-resistant bacterial infection

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424617500298 ◽

2017 ◽

Vol 21 (03) ◽

pp. 205-210 ◽

Cited By ~ 5

Author(s):

Dong Wang ◽

Yuxiang Zhang ◽

Shufeng Yan ◽

Zihan Chen ◽

Yicai Deng ◽

...

Keyword(s):

Bacterial Infections ◽

Red Light ◽

Multidrug Resistant ◽

Zinc Phthalocyanine ◽

In Vivo Studies ◽

Infection Model ◽

Clinical Test ◽

Phthalocyanine Derivative

Bacterial skin and soft tissue infections are abundant worldwide. The rise in the incidence of multidrug-resistant (MDR) bacterial infections has made the need for alternative means of treatment more pressing. We herein report a zinc phthalocyanine derivative, pentalysine [Formula: see text]-carbonylphthalocyanine zinc (ZnPc-(Lys)[Formula: see text] and its strong capability of killing nosocomial MDR bacteria, including MDR-Escherichia coli and MDR-Acinetobacter baumannii. In vitro studies, we observed that ZnPc-(Lys)5 in micromolar concentrations killed above MDR bacteria in 6~6.5 log10 orders with only 5-min illumination of red light at a dosage of 12.75 J/cm[Formula: see text]. Further in vivo studies on a mouse infection model demonstrated that ZnPc-(Lys)5 efficiently inhibited the MDR bacterial growth after one-time photodynamic antibacterial therapy and, interestingly, significantly accelerated the wound healing. Putting together, our findings establish ZnPc-(Lys)5 as a potent antimicrobial candidate for the clinical test on localized infection.

Download Full-text

Development and Evaluation of Motion-activated System for Improved Chest Drainage: Bench, In Vivo Results, and Pilot Clinical Use of Technology

Surgical Innovation ◽

10.1177/1553350620927579 ◽

2020 ◽

pp. 155335062092757

Author(s):

Jamshid H. Karimov ◽

Raymond Dessoffy ◽

Kiyotaka Fukamachi ◽

Shinji Okano ◽

Laura Idzior ◽

...

Keyword(s):

Chest Tube ◽

High Speed ◽

Flow Analysis ◽

Group Versus ◽

Control Group ◽

Clinical Test ◽

High Speed Camera ◽

In Vivo Evaluation

Objective. The aim of this study was to evaluate a motion-activated system (MAS) that applies motion-activated energy (vibration) to prevent chest tube clogging and maintain tube patency. We performed chest tube blood flow analysis in vitro, studied MAS effects on intraluminal clot deposition in vivo, and conducted a pilot clinical test. Background. Chest tube clogging is known to adversely contribute to postoperative cardiac surgery outcomes. Methods. The MAS was tested in vitro with a blood-filled chest tube model for device acceleration and performance. In vivo acute hemothorax studies (n = 5) were performed in healthy pigs (48.0 ± 2 kg) to evaluate the drainage in MAS versus control (no device) groups. Using a high-speed camera (FASTCAM Mini AX200, 100 mm Zeiss lens) in an additional animal study (n = 1), intraluminal whole-blood activation imaging of the chest tube (32 Fr) was made. The pilot clinical study (n = 12) consisted of up to a 30 minutes device tolerance test. Results. In vitro MAS testing suggested optimal device performance. The 2-hour in vivo evaluation showed a longer incremental drainage in the MAS group versus control. The total drainage in the MAS group was significantly higher than that in the control group (379 ± 144 mL vs 143 ± 40 mL; P = .0097), indicating tube patency. The high-speed camera images showed a characteristic intraluminal blood “swirling” pattern. Clinical data showed no discomfort with the MAS use (pleural = 4; mediastinal = 8). Conclusions. The MAS showed optimal performance at bench and better drainage profile in vivo. The clinical trial showed patients’ tolerance to the MAS and device safety.

Download Full-text

Transcriptome Profiling of Human Follicle Dermal Papilla Cells in response to Porphyra-334 Treatment by RNA-Seq

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6637513 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Su Yeon Kim ◽

Won Kyong Cho ◽

Hye-In Kim ◽

Seung Hye Paek ◽

Sung Joo Jang ◽

...

Keyword(s):

Hair Follicle ◽

Transcriptome Profiling ◽

Dermal Papilla ◽

Clinical Test ◽

Dermal Papilla Cells ◽

Epidermal Structure ◽

Vitro Assay

Porphyra-334 is a kind of mycosporine-like amino acid absorbing ultraviolet-A. Here, we characterized porphyra-334 as a potential antiaging agent. An in vitro assay revealed that porphyra-334 dramatically promoted collagen synthesis in fibroblast cells. The effect of porphyra-334 on cell proliferation was dependent on the cell type, and the increase of cell viability by porphyra-334 was the highest in keratinocyte cells among the three tested cell types. An in vivo clinical test with 22 participants demonstrated the possible role of porphyra-334 in the improvement of periorbital wrinkles. RNA-sequencing using human follicle dermal papilla (HFDP) cells upon porphyra-334 treatment identified the upregulation of metallothionein- (MT-) associated genes, confirming the antioxidant role of porphyra-334 with MT. Moreover, the expression of genes involved in nuclear chromosome segregation and the encoding of components of kinetochores was upregulated by porphyra-334 treatment. Furthermore, we found that several genes associated with the hair follicle cycle, the hair follicle structure, the epidermal structure, and stem cells were upregulated by porphyra-334 treatment, suggesting the potential role of porphyra-334 in hair follicle growth and maintenance. In summary, we provided several new pieces of evidence of porphyra-334 as a potential antiaging cosmetic agent and elucidated the expression network in HFDP cells upon porphyra-334.

Download Full-text