Cutibacterium acnes is an intracellular and intra-articular commensal of the human shoulder joint.

BACKGROUND: Cutibacterium acnes (C acnes) is a mysterious member of the shoulder microbiome and is associated with chronic postoperative complications and low-grade infections. Nevertheless, it is unclear whether it represents a contaminant or whether it accounts for true infections. Because it can persist intracellularly in macrophages at several body sites, it might in fact be an intra-articular commensal of the shoulder joint. METHODS: In 23 consecutive, otherwise healthy patients (17 male, 6 female; 58 years) who had no previous injections, multiple specimens were taken from the intra-articular tissue during first-time arthroscopic and open shoulder surgery. The samples were investigated by cultivation, genetic phylotyping, and immunohistochemistry using C acnes-specific antibodies and confocal laser scanning microscopy. RESULTS: In 10 patients (43.5%), cultures were C acnes-positive. Phylotype IA1 dominated the subcutaneous samples (71%), whereas type II dominated the deep tissue samples (57%). Sixteen of 23 patients (69.6%) were C acnes-positive by immunohistochemistry; in total, 25 of 40 samples were positive (62.5%). Overall, 56.3% of glenohumeral immunohistochemical samples, 62.5% of subacromial samples, and 75% of acromioclavicular (AC) joint samples were positive. In 62.5% of the tested patients, C acnes was detected immunohistochemically to reside intracellularly within stromal cells and macrophages. DISCUSSION: These data indicate that C acnes is a commensal of the human shoulder joint, where it persists within macrophages and stromal cells. Compared with culture-based methods, immunohistochemical staining can increase C acnes detection. Phylotype II seems to be most prevalent in the deep shoulder tissue. The high detection rate of C acnes in osteoarthritic AC joints might link its intra-articular presence to the initiation of osteoarthritis.

Tuberculosis of the Ankle in a Non-immunocompromised Male: A Case Report and Review of the Literature.

The prevalence and incidence of tuberculosis has declined rapidly in Western Europe during the last century, although a slight increase is being seen due to immigration from countries where tuberculosis is still a common disease. We present a very rare case of primary ankle tuberculosis in a 51-year-old native German male without any risk factors or prior lung manifestation. A delay in diagnosis and treatment when a patient presents with ankle arthritis caused by Mycobacterium tuberculosis should make one aware of the possibility of primary joint tuberculosis, which is extremely unusual and it can mimic various other joint diseases. If the diagnosis is in doubt, early biopsy should be mandatory.

Biomechanical and microbiological effects of local vancomycin in anterior cruciate ligament (ACL) reconstruction: a porcine tendon model.

INTRODUCTION: Although there is increasing evidence for the successful use of local vancomycin applied by soaked compresses during ACL reconstruction, there are still little data on its microbiological and biomechanical effects. Furthermore, exact dosage of vancomycin with respect to tendon stability and microbiological effectivity is still unknown. MATERIALS AND METHODS: 63 porcine flexor digitorum profundus tendons were harvested under sterile conditions from fresh cadaver legs. After contamination with Staphylococcus epidermidis (S. epidermidis), tendons were wrapped into sterile compresses moistened with different concentrations of vancomycin for 10 or 20 min. Sterile sodium chloride was used for control. After treatment, tendons were rolled onto blood-agar plates to test for residual bacterial contamination and tested for maximum load and stiffness using a uniaxial testing device with cryo-clamps for tendon fixation. Agar plates were checked after 1 week of culture at 36 °C for signs of bacterial growth. RESULTS: When applying vancomycin for only 10 min, bacterial contamination was found in all dosage groups ranging from 28.6% contamination (n = 2 of 7 tendons) when using 10 mg/ml up to 85.7% (n = 6 of 7 tendons) when using 1 mg/ml. Applying vancomycin-soaked compresses for 20 min, bacterial contamination was still found in the groups using 1 mg/ml and 2.5 mg/ml (contamination rate 85.7 and 42.9% respectively). When using 5 mg/ml and 10 mg/ml, no bacterial contamination could be perceived after 7 days of culture. With regard to biomechanical properties, no differences were found regarding maximum load or Young's modulus between groups. CONCLUSIONS: This study showed no signs of biomechanical impairment of porcine flexor tendons after the use of vancomycin wraps with concentration ranging from 1 to 10 mg/ml for 10 or 20 min at a time zero testing. Contamination with S. epidermidis was cleansed in 100% of tendons when using at least 5 mg/ml of vancomycin for 20 min.

Propionibacterium acnes in shoulder surgery: is loss of hair protective for infection?

BACKGROUND: Propionibacterium acnes (P acnes) has been linked to chronic infections in shoulder surgery. It was recently observed during first-time shoulder surgery in healthy patients at a rate between 36% and 56%. Male gender and the anterolateral approach were reported risk factors. Because the skin biology greatly differs, we aimed to correlate skin complaints with P acnes-positive intraoperative cultures from different tissue layer samples in patients undergoing shoulder surgery for the first time. METHODS: Intraoperative samples (1 skin, 1 superficial, 1 deep tissue, and 1 control sample) from 112 patients (70 men, 42 women; aged 59.2 years) were cultured. The association between the presence of P acnes in the deep or superficial tissue, or both, and 10 items of a validated preoperative questionnaire for skin pathology was explored. RESULTS: The cultures were positive for P acnes in 38.4% (n = 43) of the cases. Skin samples were positive for P acnes in 8% (n = 9), superficial samples were positive in 23% (n = 26), and deep samples were positive in 30% (n = 34). Self-reported "loss of hair" was significantly negatively associated with the presence of P acnes in the superficial or deep tissue sample (P = .00028). DISCUSSION: Patients who report having "loss of hair" show fewer P acnes-positive cultures in intraoperative tissue samples taken during open shoulder surgery. Whether this subgroup is at a lesser risk for P acnes infections remains to be substantiated. LEVEL OF EVIDENCE: Basic Science Study; Microbiology.

Gardening can induce pulmonary failure: Aspergillus ARDS in an immunocompetent patient, a case report.

BACKGROUND: Acute Aspergillus fumigatus infection in immunocompetent patients is rare. This is the first known case of a patient who survived Aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ECMO) and antifungal therapy. CASE PRESENTATION: An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure. Owing to her severe clinical condition, she was treated for acute respiratory distress syndrome (ARDS) with veno-venous ECMO. Empiric antifungal therapy comprising voriconazole was also initiated owing to her history and a previous case report of aspergillosis after plant mulch exposure, though there was no microbiological proof at the time. A. fumigatus was later cultured and detected on antibody testing. The patient recovered, and ECMO was discontinued 1 week later. After 7 days of antifungal treatment, Aspergillus antibodies were undetectable. CONCLUSIONS: In cases of sepsis that occur after gardening, clinicians should consider Aspergillus inhalation as an aetiology, and early antimycotic therapy is recommended.

Propionibacterium acnes in shoulder surgery: true infection, contamination, or commensal of the deep tissue?

BACKGROUND: Propionibacterium acnes has been linked to chronic infections in shoulder surgery. Whether the bacterium is a contaminant or commensal of the deep tissue is unclear. We aimed to assess P. acnes in intraoperative samples of different tissue layers in patients undergoing first-time shoulder surgery. METHODS: In 118 consecutive patients (mean age, 59.2 years; 75 men, 43 women), intraoperative samples were correlated to preoperative subacromial injection, the type of surgical approach, and gender. One skin, one superficial, one deep tissue, and one test sample were cultured for each patient. RESULTS: The cultures were positive for P. acnes in 36.4% (n = 43) of cases. Subacromial injection was not associated with bacterial growth rates (P = .88 for P. acnes; P = .20 for bacteria other than P. acnes; P = .85 for the anterolateral approach; P = .92 for the deltopectoral approach; P = .56 for men; P = .51 for women). Skin samples were positive for P. acnes in 8.5% (n = 10), superficial samples were positive in 7.6% (n = 9), deep samples were positive in 13.6% (n = 16), and both samples (superficial and deep) were positive in 15.3% (n = 18) of cases (P < .0001). P. acnes was detected in the anterolateral approach in 27.1% (n = 32) of cases and in the deltopectoral approach in 9.3% (n = 11) of cases (P = .01; relative risk, 1.93; 95% confidence interval, 1.08-3.43). Thirty-five of the P. acnes-positive patients were men (81.4%), and 8 patients were women (18.6%; P = .001; relative risk, 2.51; 95% confidence interval, 1.28-4.90). DISCUSSION: P. acnes was detected in more than one third of patients undergoing first-time shoulder surgery. Preoperative subacromial injection was not associated with bacterial growth. P. acnes was observed more frequently in the deep tissues than in the superficial tissues. The relative risk for obtaining a positive P. acnes culture was 2-fold greater for the anterolateral approach than for the deltopectoral approach, and the risk was 2.5-fold greater for men.

CYP19A1 mediates severe SARS-CoV-2 disease outcome in males.

Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n = 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment.

Synergistic In Vitro Interaction of Isavuconazole and Isoquercitrin against Candida glabrata.

In vitro interactions of broad-spectrum azole isavuconazole with flavonoid isoquercitrin were evaluated by a broth microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference methodology for antifungal susceptibility testing against 60 Candida strains belonging to the species Candida albicans (n = 10), Candida glabrata (n = 30), Candida kefyr (n = 6), Candida krusei (n = 5), Candida parapsilosis (n = 4), and Candida tropicalis (n = 5). The results were analyzed with the fractional inhibitory concentration index and by response surface analysis based on the Bliss model. Synergy was found for all C. glabrata strains, when the results were interpreted by the fractional inhibitory concentration index, and for 60% of the strains when response surface analysis was used. Interaction for all other species was indifferent for all strains tested, whatever interpretation model used. Importantly, antagonistic interaction was never observed.

In Vitro Synergy of Isavuconazole Combined With Colistin Against Common Candida Species.

Interactions of isavuconazole and colistin were evaluated against 57 common Candida strains belonging to the species Candida albicans (n = 10), Candida glabrata (n = 10), Candida kefyr (n = 8), Candida krusei (n = 10), Candida parapsilosis (n = 9), and Candida tropicalis (n = 10) by a broth microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference methodology for antifungal susceptibility testing. Results were analyzed with the fractional inhibitory concentration index and by the response surface analysis. Interpretation by the fractional inhibitory concentration index showed synergy for 50%, 80%, 90%, and 90% of the C. kefyr, C. krusei, C. glabrata, and C. tropicalis strains, respectively. Combination of isavuconazole with colistin against C. albicans and C. parapsilosis exhibited only indifference for 100% and 90% of the strains, respectively. The results were confirmed by response surface analysis for all species except for C. glabrata, for which an indifferent interaction was found for the majority of strains. Antagonistic interaction was never seen regardless of the interpretation model was used.

In Vitro Activity of Amphotericin B in Combination with Colistin against Fungi Responsible for Invasive Infections.

The in vitro interaction of amphotericin B in combination with colistin was evaluated against a total of 86 strains comprising of 47 Candida species (10 Candida albicans, 15 Candida auris, five Candida glabrata, three Candida kefyr, five Candida krusei, four Candida parapsilosis and five Candida tropicalis), 29 Aspergillus species (five Aspergillus flavus, 10 Aspergillus fumigatus, four Aspergillus nidulans, five Aspergillus niger, and five Aspergillus terreus), and 10 Rhizopus species (seven Rhizopus arrhizus, one Rhizopus delemar and two Rhizopus microsporus) strains. For the determination of the interaction, a microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method for antifungal susceptibility testing was used. Results of the checkerboard technique were evaluated by the fractional inhibitory concentration index (FICI) based on the Loewe additivity model for all isolates. Different inhibition endpoints were used to capture both the interaction at MIC and sub-MIC levels. Additionally, checkerboard technique results for Candida species were evaluated by response surface analysis based on the Bliss independence model. Against common Candida species, the combination was synergistic for 75% of the strains by FICI and for 66% of the strains by response surface analysis. For C. tropicalis, the interaction was antagonistic for three isolates by FICI, but antagonism was not confirmed by response surface analysis. Interestingly, synergistic and antagonistic FICIs were simultaneously present on checkboard microplates of all three strains. Against C. auris the combination was synergistic for 73% of the strains by response surface analysis and for 33% of the strains by FICI. This discrepancy could be related to the insensitivity of the FICI to detect weak interactions. Interaction for all other strains was indifferent. For Aspergillus and Rhizopus species combination exhibited only indifferent interactions against all tested strains.

Complete Genome Sequences of Two Nosocomiicoccus ampullae Strains and a Growth-Adapted Mutant.

Here, we present the circular and complete genome sequences of the Nosocomiicoccus ampullae isolate 19-00310 and type strain DSM 19163. To our knowledge, these represent the first complete, circular chromosomes in the entire genus. Sequencing of a growth-adapted mutant suggests iron availability as a factor for growth improvement.

Enhanced TCR-induced apoptosis in interferon regulatory factor 4-deficient CD4(+) Th cells.

Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4(+) T helper (Th) cells lacking IRF4 (IRF4(-/-)) are highly sensitive to apoptosis. After infection of IRF4(-/-) mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4(-/-) CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4(+) cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4(-/-) and IRF4(+/+) cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+) cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central in protecting CD4(+) cells against proapoptotic stimuli.

The history of female ejaculation.

INTRODUCTION: The existence of female ejaculation and the female prostate is controversial; however, most scientists are not aware that historians of medicine and psychology described the phenomenon of female ejaculation approximately 2,000 years ago. AIM: To review historical literature in which female ejaculation is described. METHODS: A comprehensive systematic literature review. MAIN OUTCOME MEASURE: Emission of fluid at the acme of orgasm and/or sexual pleasure in females was considered as a description of female ejaculation and therefore all documents referring to this phenomenon are included. RESULTS: Physicians, anatomists, and psychologists in both eastern and western culture have described intellectual concepts of female ejaculation during orgasm. In ancient Asia female ejaculation was very well known and mentioned in several Chinese Taoist texts starting in the 4th century. The ancient Chinese concept of female ejaculation as independent of reproduction was supported by ancient Indian writings. First mentioned in a 7th century poem, female ejaculation and the Gräfenberg spot (G-spot) are described in detail in most works of the Kamasastra. In ancient Western writings the emission of female fluid is mentioned even earlier, depicted about 300 B.C. by Aristotle and in the 2nd century by Galen. Reinjier De Graaf in the 16th century provided the first scientific description of female ejaculation and was the first to refer to the periurethral glands as the female prostate. This concept was held by other scientists during the following centuries through 1952 A.D. when Ernst Gräfenberg reported on "The role of the urethra in female orgasm. Current research provides insight into the anatomy of the female prostate and describes female ejaculation as one of its functions. CONCLUSIONS: Credible evidence exists among different cultures that the female prostate and female ejaculation have been discovered, described and then forgotten over the last 2,000 years.

Bicycle riding and erectile dysfunction: a review.

INTRODUCTION: For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications. AIM: To review current literature on the rationale for ED from bicycle riding and outcome of bicycle riding on erectile function and to present available research on preventative measures specifically regarding bicycle riding. METHODS: A systematic comprehensive literature review. RESULTS: There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists. Preventative measures including use of a properly fitted bicycle, a riding style with a suitable seat position and an appropriate bicycle seat can help prevent impairment of erectile function. CONCLUSIONS: There is a need for further research on safe bicycle and bicycle seat design and investigations that address the underlying mechanisms leading to cycling-related sexual dysfunction in both male and female bicyclists.

Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence.

OBJECTIVE: To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and rigidity (NPTR, RigiScan), given nightly for 1 year, can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED); this regimen was compared with a fixed daily dosage of sildenafil 25 mg or vardenafil 5 mg. PATIENTS AND METHODS: In a prospective open-label, parallel-group trial 154 men with ED were randomized either to fixed low-dose sildenafil 25 mg or vardenafil 5 mg (group 1) or to the lowest erectile dosage of sildenafil (25, 50 or 100 mg) or vardenafil (5, 10 or 20 mg) (group 2) provoking an erectile event as measured by NPTR nightly for 1 year. The EF domain of the International Index of Erectile Function (IIEF) was assessed before and 1 year after the beginning of treatment, and at 4 weeks after ending treatment. RESULTS: After 1 year, 27 of 63 (64%) evaluable men in group 1 had an EF domain score in the normal range, vs 46 of 61 (75%) men in group 2. After the subsequent 4-week wash-out phase, both groups continued to have improved EF domain scores; 22 of 63 (35%) men in group 1 still had a score in the normal range, whereas 38 of 61 (62%) in group 2 had a normal score. The EF domain score in group 1 and 2 improved significantly after 1 year of treatment, from 13.6 to 18.9, and 15.1 to 23.9, respectively (P < 0.01). After the subsequent 4-week wash-out phase, men from both groups maintained this significant level of EF, at 17.1 and 22.4, respectively (P < 0.05). CONCLUSION: Nightly PDE5-inhibitor treatment 1 year in a dosage determined by NPTR measurements results in better EF than giving a fixed dosage of sildenafil (25 mg) or vardenafil (5 mg). This improvement persisted for >4 weeks beyond the end of treatment. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial.

AIM: To test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment. METHODS: In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy. RESULTS: After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized. CONCLUSION: Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Evaluation of tetrahydrobiopterin (BH4) as a potential therapeutic agent to treat erectile dysfunction.

AIM: Nitric oxide (NO)-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase (eNOS) coenzyme tetrahydrobiopterin (BH4) converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation. METHODS: Using quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction (ED) while receiving visual sexual stimulation. RESULTS: 8-Isoprostane content in endothelium and smooth muscle was significantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of > 60% penile rigidity (33.5 min [95% confidence interval (CI): 13.1-49.3] at base and 29.4 min [95% CI: 8.9-42.2] at tip). A 500-mg dose increased the relative duration of > 60% penile rigidity by 36.1 min (95% CI: 16.3-51.8) at the base and 33.7 min (95% CI: 11.4-43.9) at the tip. Treatments were well tolerated. CONCLUSION: BH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS.

Covalent immobilization of lysozyme onto woven and knitted crimped polyethylene terephthalate grafts to minimize the adhesion of broad spectrum pathogens.

Graft-associated infections entirely determine the short-term patency of polyethylene terephthalate PET cardiovascular graft. We attempted to enzymatically inhibit the initial bacterial adhesion to PET grafts using lysozyme. Lysozyme was covalently immobilized onto woven and knitted forms of crimped PET grafts by the end-point method. Our figures of merit revealed lysozyme immobilization yield of 15.7 µg/cm(2), as determined by the Bradford assay. The activity of immobilized lysozyme on woven and knitted PET manifested 58.4% and 55.87% using Micrococcus lysodeikticus cells, respectively. Noteworthy, the adhesion of vein catheter-isolated Staphylococcus epidermidis decreased by 6- to 8-folds and of Staphylococcus aureus by 11- to 12-folds, while the Gram-negative Escherichia coli showed only a decrease by 3- to 4-folds. The anti-adhesion efficiency was specific for bacterial cells and no significant effect was observed on adhesion and growth of L929 cells. In conclusion, immobilization of lysozyme onto PET grafts can inhibit the graft-associated infection.

Potency and selectivity of vardenafil: a phosphodiesterase Type 5 inhibitor.

Erectile dysfunction (ED) is a widespread, age-related medical condition that affects > 50% of men aged 40 - 70 years. Pharmacotherapy with orally available phosphodiesterase 5 (PDE5) inhibitors offers a convenient and simple approach to treatment. Results of numerous clinical trials have demonstrated significant efficacy in restoring the ability to achieve and sustain an erection, and adverse side effects are generally mild-to-moderate in severity. Vardenafil is a highly selective, potent PDE5 inhibitor developed for the treatment of ED. The potency and selectivity of vardenafil for PDE5 and other PDE isoforms have been evaluated in vitro and in vivo and compared with other compounds in the class. This review will discuss the findings of biochemical, in vitro and in vivo experiments that indicate the superior potency and high selectivity of vardenafil.

Multifunctional network-structured film coating for woven and knitted polyethylene terephthalate against cardiovascular graft-associated infections.

Multifunctional network-structured polymeric coat for woven and knitted forms of crimped polyethylene terephthalate PET graft was developed to limit graft-associated infections. A newly synthesized antibacterial sulfadimethoxine polyhexylene adipate-b-methoxy polyethylene oxide (SD-PHA-b-MPEO) di-block copolymer was employed. Our figures of merit revealed that the formed coat showed a porous topographic architecture which manifested paramount properties, mostly bacterial anti-adhesion efficiency and biocompatibility with host cells. Compared to untreated grafts, the coat presented marked reduction of adhered Gram-positive Staphylococcus epidermidis previously isolated from a patient's vein catheter by 2.6 and 2.3 folds for woven and knitted grafts, respectively. Similarly, bacterial anti-adhesion effect was observed for Staphylococcus aureus by 2.3 and 2.4 folds, and by 2.9 and 2.7 folds for Gram-negative Escherichia coli for woven and knitted grafts, respectively. Additionally, adhesion and growth characteristics of L929 cells on the modified grafts revealed no significant effect on the biocompatibility. In conclusion, coating of PET with (SD-PHA-b-MPEO) is a versatile approach offers the desired bacterial anti-adhesion effect and host biocompatibility.