Antibacterial and Antibiofilm Activity of Endophytic Alternaria sp. Isolated from Eremophila longifolia.

The threat to public health resulting from the emergence of antimicrobial resistance (AMR) is ever rising. One of the major bacterial pathogens at the forefront of this problem is methicillin-resistant Staphylococcus aureus, or MRSA, for which there is a great need to find alternative treatments. One of the most promising alternatives is endophytic fungi, which were shown to produce a vast array of bioactive compounds, including many novel antibacterial compounds. In this study, two endophytic Alternaria sp., EL 24 and EL 35, were identified from the leaves of Eremophila longifolia. Ethyl acetate (EtOAc) extracts of their culture filtrates were found to inhibit both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. The activity of each extract was shown to be greatly affected by the growth medium, with considerable reductions in minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) observed when tested in tryptic soy broth with glucose (TSBG) compared with Mueller-Hinton broth (MHB). Both extracts displayed significant (p ≤ 0.05) antibiofilm activity against all three S. aureus strains, the greatest of which was that of EL 35, which reduced biofilm formation by M180920 by 72%, while that of EL 24 resulted in a 57% reduction against ATCC 25923. Both extracts also disrupted established biofilms, of which the most effective was EL 35, which reduced the M180920 biofilm by 64%, while EL 24 also performed best against M180920, reducing biofilm by 54%. Gas chromatography-mass spectrometry (GC-MS) analysis of the EL 24 EtOAc extract revealed five known compounds. This study highlights the promise of endophytic fungi from Australian plants as a potential source of substances effective against important bacterial pathogens. Further understanding of the responsible compounds and their mechanisms could lead to the development of treatments effective against MRSA, as well as novel biofilm-resistant biomedical materials, contributing towards reducing the burden of AMR.

Exploring the Promise of Endophytic Fungi: A Review of Novel Antimicrobial Compounds.

Over the last few decades, many of the existing drugs used to treat infectious diseases have become increasingly ineffective due to the global emergence of antimicrobial resistance (AMR). As such, there is a constant demand to find new, effective compounds that could help to alleviate some of this pressure. Endophytic fungi have captured the attention of many researchers in this field, as they have displayed a vast ability to produce novel bioactive compounds, many of which possess wide-ranging antimicrobial activities. However, while highly promising, research in this area is still in its infancy. Endophytes inhabit the healthy tissues of plants asymptomatically, resulting in a mutualistic symbiosis in which the endophytes produce a plethora of bioactive compounds that support the fitness of the host plant. These compounds display great chemical diversity, representing structural groups, such as aliphatic compounds, alkaloids, peptides, phenolics, polyketides and terpenoids. In this review, the significant antimicrobial potential of endophytic fungi is detailed, highlighting their ability to produce novel and diverse antimicrobial compounds active against human, plant and marine pathogens. In doing so, it also highlights the significant contributions that endophytic fungi can make in our battle against AMR, thus providing the motivation to increase efforts in the search for new and effective antimicrobial drugs.

Role of botulinum toxin-A in refractory idiopathic overactive bladder patients without detrusor overactivity.

BACKGROUND: To evaluate the efficacy of intradetrusor botulinum toxin-A (BTX-A) in idiopathic overactive bladder patients (OAB) refractory to anti-muscarinic therapy, without detrusor overactivity (DOA) on urodynamics. METHODS: Patients with refractory idiopathic OAB without DOA on urodynamics were prospectively enrolled. Subjects completed a 3-day voiding diary (3-VD), urogenital distress inventory-6 questionnaire (UDI-6) and graded their quality of life on a 10-cm visual analog scale (VAS) prior to study enrollment and at week 12 postinjection. All patients underwent multichannel urodynamics at study enrollment and 12 weeks postinjection. Improvement was analyzed based on 3-VD, UDI-6 questionnaire, VAS scores, and urodynamic parameters at week 12 postinjection compared to study enrollment. RESULTS: The study included 32 patients. Mean ± SD age was 56 ± 16. There were 27 women and 5 men. Nineteen patients had OAB without incontinence (OAB-dry) and 13 patients had OAB with incontinence (OAB-wet). In OAB-dry patients, mean ± SD urinary frequency dropped from 24 ± 11 to 10 ± 4 by week 12. In OAB-wet patients, mean ± SD urge incontinence episodes dropped from 7.9 ± 5 to 0 ± 2.6 by week 12. Mean UDI-6 and VAS scores improved significantly in both groups by week 12 (P = 0.0001). On comparing urodynamic parameters, OAB-wet patients showed significant decrease in maximum detrusor pressure during the voiding phase at week 12 compared to baseline values (P = 0.02). CONCLUSIONS: Refractory idiopathic OAB patients without DOA on urodynamics may benefit from intradetrusor BTX-A.

Differentiation of oncocytoma and renal cell carcinoma in small renal masses (<4 cm): the role of 4-phase computerized tomography.

PURPOSE: We investigate the use of 4-phase computerized tomography with intravenous contrast to help distinguish oncocytoma from renal cell carcinoma (RCC) in tumors <4 cm. METHODS: We retrospectively identified patients who underwent surgical management for renal tumors <4 cm from 2005 to 2008. Patients who had pre-operative CT evaluation as per our institution's renal mass protocol and had confirmed pathological diagnosis of either oncocytoma or RCC were included in the study. Enhancement readings were obtained for the tumor and the renal cortex using the same slice simultaneously. RESULTS: Our cohort involved 69 patients (46 men, 23 women; mean age 66) who presented with 79 renal masses. Histopathologically 40 were clear cell, 22 papillary, 5 chromophobe RCC and 12 oncocytoma. On the arterial, venous and delayed phase images, oncocytoma showed the highest mean enhancement change, i.e.,546, 396 and 239% followed by clear cell RCC 261, 261 and 174%, chromophobe RCC 147, 127 and 66% and papillary RCC 137, 184 and 118%, respectively. The enhancement pattern differed significantly on comparing oncocytoma with RCC (P < 0.007). The mean percentage contrast excreted at the end of the delayed phase was 33.3, 13.8, 32 and 53% for clear cell, papillary, chromophobe and oncocytoma, respectively. CONCLUSION: The enhancement and washout values in Hounsfield units obtained by multiphasic CT scan aid in distinguishing oncocytoma from the commonly seen subtypes of RCC in renal masses <4 cm. This preliminary study demonstrates that arterial phase enhancement greater than 500% and washout values of greater than 50% are exclusively seen in renal oncocytomas.

What is the predictive value of urodynamics to reproduce clinical findings of urinary frequency, urge urinary incontinence, and/or stress urinary incontinence?

INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the predictive value of urodynamics to reproduce clinical findings of urinary frequency (UF), urge urinary incontinence (UUI), and/or stress urinary incontinence (SUI). METHODS: We retrospectively reviewed the data of patients diagnosed with UF, UUI, and/or SUI and subsequently underwent urodynamics. Urodynamic findings were correlated with clinical findings to determine the predictive value of urodynamics. RESULTS: A total of 537 patients (366 females and 171 males) met study criteria. Two hundred seventy-eight patients had symptoms of UUI; 59% demonstrated detrusor overactivity on urodynamics. Three hundred eight patients had SUI on history and physical examination; 45% had urodynamic stress incontinence. A low maximum cystometric capacity (<200 ml) was not significantly associated with urinary frequency (p = 0.4). CONCLUSIONS: Urodynamics has a low predictive value to reproduce clinical findings of UF, UUI, and/or SUI. Many patients with evidence of UF, UUI, and/or SUI on history and/or physical examination do not demonstrate supporting urodynamic evidence.

Predictors of response to intradetrusor botulinum toxin-A injections in patients with idiopathic overactive bladder.

OBJECTIVES: To evaluate whether there are any demographic or urodynamic differences in patients with idiopathic overactive bladder (I-OAB) that respond and do not respond to intradetrusor injections of botulinum toxin-A (BTX-A). METHODS: This represents a secondary analysis of data collected from an investigator initiated randomized trial designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Preinjection demographic and urodynamic data were collected. Patients were evaluated 12 weeks after injection and were determined to be responders or nonresponders as defined by our criteria. Statistical comparisons were made between groups. RESULTS: In patients with overactive bladder without incontinence (OAB-Dry), there were no variables that could be used to predict response to BTX-A. On univariate analysis, younger patients with overactive bladder with incontinence (OAB-Wet) were more likely to respond to BTX-A than older patients. However, this relationship was no longer statistically significant on multivariate analysis. CONCLUSIONS: We were unable to identify any preinjection demographic or urodynamic parameters that could aid in predicting which patients will achieve clinical response to BTX-A. Future studies are necessary to further evaluate this question.

Medical management of stress urinary incontinence: is there a future?

Stress urinary incontinence (SUI) is a common problem among women worldwide. Multiple treatment modalities exist, ranging from physiotherapy to surgery. Numerous reports demonstrate mixed results for efficacy and safety of several oral agents used to treat SUI. Although there are data suggesting reasonable efficacy for several medications, surgery still remains the mainstay of treatment for most women. This article reviews the available oral agents that have been studied and assesses the data supporting their use while highlighting the limitations of each.

Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence.

PURPOSE: Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression. EXPERIMENTAL DESIGN: Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models. RESULTS: In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 +/- 78.4; 181.1 +/- 89.3) than in the nonrecurred group (122.7 +/- 76.6; 96.4 +/- 85.6; P < 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P < 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%). CONCLUSION: In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.

Anatomic variants associated with newborn circumcision complications.

OBJECTIVE: Circumcision is one of the commonly performed procedures on males in the United States, Canada, Australia, and the United Kingdom. The association of minor anatomic variations of the newborn genitalia in patients with minor circumcision complications has not been previously examined. In this study, we looked for an association between subtle genital anatomic variations and newborn circumcision complications. MATERIALS AND METHODS: Over an 18-month period, children presenting for circumcision revision were examined for minor variations in genital anatomy. Children referred for other urological problems during the same period comprised the control group. The same physician evaluated all of the children. RESULTS: During this period, 68 children were evaluated for possible circumcision complications. A confirmed complication was present in 57 infants. Patients with a minor circumcision complication were found to have a 9-fold higher incidence of a prominent suprapubic fat pad, penoscrotal webbing, or being a premature infant as compared to the control group. CONCLUSIONS: Subtle anatomic variations may be associated with a higher incidence of circumcision complications. Physicians performing newborn circumcisions should thoroughly examine the genitalia for these anatomic variations prior to the procedure in order to reduce potential complications.

Urinary ascites secondary to forniceal rupture in a child with the Prune Belly Syndrome.

Despite adequate bladder catheterization, a neonate with Prune Belly Syndrome developed urinary ascites secondary to forniceal rupture. Treatment consisted of bilateral cutaneous pyelostomies. Even though most children with Prune Belly Syndrome respond to lower urinary tract drainage, a cutaneous pyelostomy may be necessary when the ureters are tortuous and do not drain adequately following bladder decompression.